111 results on '"Robinson PD"'
Search Results
2. Utilising Hem-o-lok® ligation system to safely and efficiently divide bilioenteric fistulae in laparoscopic cholecystectomy
- Author
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Finch, LM, primary, Robinson, PD, additional, and Szentpali, K, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age
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Martins Costa Gomes, G, de Gouveia Belinelo, P, Starkey, MR, Murphy, VE, Hansbro, PM, Sly, PD, Robinson, PD, Karmaus, W, Gibson, PG, Mattes, J, and Collison, AM
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1107 Immunology, 1115 Pharmacology and Pharmaceutical Sciences - Abstract
Objective: Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10-fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Methods: Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t-distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Results: Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty-four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor-homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age." Conclusion: Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life.
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- 2021
4. Unique subpopulations of cord blood innate lymphoid cells are associated with lung function at 6 weeks of age in babies born to mothers with asthma during pregnancy
- Author
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Gomes, GMC, Belinelo, PG, Starkey, MR, Jesson, K, Loering, S, Hansbro, PM, Murphy, VE, Hardaker, K, Robinson, PD, Sly, PD, Gibson, PG, Mattes, J, and Collison, AM
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Allergy - Published
- 2019
5. Enhanced recovery after anterior resection: earlier leak diagnosis and low mortality in a case series
- Author
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D’Souza, N, primary, Robinson, PD, additional, Branagan, G, additional, and Chave, H, additional
- Published
- 2019
- Full Text
- View/download PDF
6. Utilising Hem-o-lok® ligation system to safely and efficiently divide bilioenteric fistulae in laparoscopic cholecystectomy.
- Author
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Finch, LM, Robinson, PD, and Szentpali, K
- Published
- 2023
- Full Text
- View/download PDF
7. Enhanced recovery after anterior resection: earlier leak diagnosis and low mortality in a case series.
- Author
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D'Souza, N, Robinson, PD, Branagan, G, and Chave, H
- Published
- 2019
- Full Text
- View/download PDF
8. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone
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Stempel, Da, Raphiou, Ih, Kral, Km, Yeakey, Am, Emmett, Ah, Prazma, Cm, Buaron, Ks, Pascoe, Sj, Austri, Investigators, Altieri, Hh, Antuni, Jd, Bergna, Ma, Cuadrado, Ja, De Gennaro MS, Fazio Lizandrelo CL, Gattolin, G, Gosn, Am, Larrateguy, Ld, Marcipar, Am, Maspero, Jf, Medina, Iv, Perez Chada RD, Silva, D, Victorio, Cf, Bardin, Pg, Carroll, Pa, Clements, Bs, Dore, Nd, Robinson, Pd, Fitzgerald, Da, Robinson, Pj, Russo, Ma, Sajkov, D, Thomas, Ps, Upham, Jw, Forstner, B, Kaik, G, Koeberl, Gh, Studnicka, M, Wallner, G, Balthazar, Y, Bauler, A, Dupont, Lj, Martinot, Jb, Ninane, V, Peché, R, Pilette, C, Dimitrova, R, Dimova, D, Kissyova Ibrishimova, G, Loboshka Becheva, M, Machkovska, M, Madjarov, S, Mandazhieva Pepelanova, M, Naidenova, I, Noleva, K, Takovska, N, Terziev, C, Aggarwal, Nk, Chapman, Kr, Csanadi, Ma, Dhillon, R, Henein, S, Kelly, Aj, Lam, As, Liem, Jj, Lougheed, Md, Lowe, Dw, Rizvi, Q, van den Berg, L, Zidel, B, Barros Monge MJ, Calvo Gil MA, Castillo Hofer CR, Diaz Amor PV, Lezana Soya, V, Quilodran Silva CN, Bolivar Grimaldos, F, Solarte-Rodriguez, I, Butkovic-Tomljanovic, R, Hegedus-Jungvirth, M, Ivkovic-Jurekovic, I, Simunov-Karuza, G, Buresova, M, Bursova, J, Fratrik, J, Guttlerova, E, Hartman, P, Jirmanova, I, Kalina, P, Kolman, P, Kucera, M, Povysilova, L, Pravda, P, Svabkova, A, Zakova, L, Backer, V, Maltbaek, N, Johnsen, Cr, Aries, Sp, Babyesiza, A, Barth, D, Benedix, A, Berg, P, Bergtholdt, B, Bettig, U, Bindig, Hw, Botzen, U, Brehler, R, Breyer, Go, Bruckhaus-Walter, M, Dapper, T, Eckhard, Jg, Engelhard, R, Feldmeyer, F, Fissan, H, Franz, Kh, Frick, Bs, Funck, J, Gessner, Cm, Ginko, T, Grigat, Ce, Grimm-Sachs, V, Groth, G, Hampf, J, Hanf, G, Havasi-Jost, G, Heinz, Gu, Helm, K, Hoeltz, S, Hofmann, S, Jander, R, Jandl, M, Jasch-Hoppe, B, Jung, T, Junggeburth, Jj, Kardos, P, Knueppel, W, Koch, T, Kolorz, C, Korduan, M, Korth-Wiemann, B, Krezdorn, Hg, Kroker, A, Kruell, M, Kuehne, P, Lenk, U, Liefring, E, Merke, J, Micke, L, Mitlehner, W, Mueller, H, Naudts, If, Neumann, G, Oldenburg, W, Overlack, A, Panzer, F, Reinholz, N, Remppis, R, Riegel, P, Rueckert, P, Schaetzl, Rj, Schauer, U, Hamelmann, E, Schenkenberger, I, Schlegel, V, Scholz, G, Schroers, M, Schwittay, A, Sebert, M, Tyler, K, Soemantri, Pa, Stock, P, Stuchlik, G, Unland, M, von Mallinckrodt, C, Wachter, J, Weber, U, Weberling, F, Wehgartner-Winkler, S, Weimer, J, Wiemer, S, Winkelmann, Ej, Zeisler, Kh, Ziegner, A, Zimny, Hh, Andrasofszky, Z, Bartha, A, Farkas, M, Gömöri, K, Kis, S, Major, K, Mészáros, I, Mezei, M, Rakvacs, M, Szalai, Z, Szántó, J, Szentesi, M, Szolnoki, E, Valyon, E, Zibotics, H, Anwar, J, Arimah, C, Djajalaksana, S, Rai, Ib, Setijadi, Ar, Setyanto, Db, Susanti, F, Syafiuddin, T, Syamsi, Ln, Wijanarko, P, Yunus, F, Bonavia, M, Braga, M, Chetta, Aa, Cerveri, I, Luisetti, M, Crimi, N, Cutrera, R, De Rosa, M, Esposito, S, Foresi, A, Gammeri, E, Iemoli, E, Legnani, Dl, Michetti, G, Pastorello, Ea, Pesci, A, Pistolesi, M, Riva, E, Romano, A, Scichilone, N, Terracciano, L, Tripodi, S, Choi, I, Kim, C, Kim, Js, Kim, Wj, Koh, Yy, Kwon, Ss, Lee, Sh, Lee, S, Lee, Sk, Park, Cs, Cirule, I, Eglite, R, Petrova, I, Poga, M, Smiltena, I, Chomiciene, A, Davoliene, I, Griskeviciene, V, Naudziunas, A, Naudziunas, S, Rudzeviciene, O, Sitkauskiene, B, Urbonas, G, Vaicius, D, Valavicius, A, Valiulis, A, Vebriene, J, bin Abdul Aziz FA, Daud, M, Ismail, Ai, Tengku Saifudin TI, Md Kassim RM, Mohd Fadzli FB, Wan Mohamad WH, Aguilar Dominguez PE, Aguilar-Orozco, Ra, Garza-Salinas, S, Ramirez-Diaz, Sp, Sánchez Llamas, F, Soto-Ramos, M, Velarde-Mora, Hj, Aguirre Sosa, I, Cisneros, Am, Estrella Viladegut RA, Matsuno Fuchigami, A, Adiaz-Baui, Tt, Bernan, Ap, Onia, Af, Sandagon, Mj, S-Naval, S, Yu, Cy, Bartuzi, Z, Bielous-Wilk, A, Błażowski, Ł, Bożek, A, Brzostek, J, Chorostowska-Wynimko, J, Ciekalska, K, Ziora, D, Cieslicki, J, Emeryk, A, Folcik, K, Gałuszka-Bilińska, A, Gawlik, R, Giejlo, M, Harat, R, Hofman, T, Jahnz-Różyk, K, Jedrzejczak, M, Kachel, T, Kamiński, D, Kelm Warchol, A, Konieczny, Z, Kwasniewski, A, Leszczyński, W, Mincewicz, G, Niezgoda, K, Olszewska-Ziąber, A, Onasz-Manitius, M, Pawlukiewicz, M, Piotrowicz, P, Piotrowski, W, Pisarczyk-Bogacka, E, Piskorz, P, Prokop-Staszecka, A, Roslan, A, Słomka, A, Smalera, E, Stelmach, I, Swierczynska-Krepa, M, Szmidt, M, Tarnowska-Matusiak, M, Tłuczykont, B, Tyminska, K, Waszkuc-Golonko, J, Wojciechowska, I, Alexandrescu, Ds, Neamtu, Ml, Todea, D, Alekseeva, E, Aleksandrova, E, Asherova, I, Barbarash, Ol, Bugrova, O, Bukreeva, Eb, Chermenskiy, A, Chizhova, O, Demko, I, Evdokimova, A, Giorgadze, Ml, Grigoryev, S, Irkhina, I, Khurkhurova, Nv, Kondyurina, Eg, Kostin, Vi, Kudelya, L, Laleko, Sl, Lenskaya, L, Levashov, S, Logvinenko, N, Martynov, A, Mizernitski, Y, Nemtsov, B, Novozhenov, Vg, Pavlishchuk, S, Popova, Vv, Reshetko, Ov, Sherenkov, A, Shirinsky, Vs, Shpagina, L, Soloviev, Ki, Tkachev, A, Trofimov, Vi, Vertkin, Al, Vorobeva, E, Idrisova, E, Yakushin, S, Zadionchenko, V, Zhiglinskaya, O, Zykov, K, Dopudja Pantic, V, Nadaskic, R, Nestorovic, B, Skodric Trifunovic, V, Stojanovic, A, Vukcevic, M, Vujic, T, Mitic Milikic, M, Banovcin, P, Horvathova, H, Karako, P Sr, Plutinsky, J, Pribulova, E, Szarazova, M, Zlatos, A, Adams, L, Badat, A, Bassa, A, Breedt, J, Bruning, A, Ellis, Gc, Emanuel, S, Fouche, Lf, Fulat, Ma, Gani, M, Ismail, Ms, Jurgens, Jc, Nell, H, Nieuwoudt, G, Noor, F, Bolliger, Ct, Puterman, As, Siddique, N, Trokis, Js, Vahed, Ya, Van Der Berg BJ, Van der Linden, M, Van Zyl, L, Visser, Ss, Antépara Ercoreca, I, Arnedillo Muñoz, A, Barbe Illa, F, Barreiro López, B, Blanco Aparicio, M, Boada Valmaseda, A, Bosque García, M, Bustamante Ruiz, A, Carretero Anibarro, P, Del Campo Matias, F, Echave-Sustaet, Jm, Espinosa de los Monteros Garde MJ, Garcia Hernandez GM, López Viña, A, Lores Obradors, L, Luengo Planas MT, Monsó Molas, E, Navarro Dourdil, A, Nieto García AJ, Perpina Tordera, M, Picado Valles, C, Rodriguez Alvarez Mdel, M, Saura Vinuesa, A, Serra Batlles, J, Soler Sempere MJ, Toran Montserrat, P, Valdés Cuadrado LG, Villasante Fernandez-Montes, C, Cheng, Sl, Chern, Jh, Chiu, Mh, Chung, Cl, Lai, Rs, Lin, Ck, Liu, Yc, Wang, Cc, Wei, Yf, Amer, L, Berenfus, Vi, Besh, L, Duka, Kd, Fushtey, Im, Garmash, N, Dudnyk, O, Godlevska, O, Vlasenko, Ma, Hospodarskyy, I, Iashyna, L, Kaladze, M, Khvelos, Si, Kostromina, Vp, Krakhmalova, O, Kryuchko, T, Kulynych, Ov, Krasko, Mp, Levchenko, O, Litvinova, T, Panina, Ss, Pasiyeshvili, Lm, Prystupa, Ln, Romaniuk, Li, Sirenko, I, Synenko, Vi, Vynnychenko, Lb, Yatsyshyn, Ri, Zaitsev, I, Zhebel, V, Zubarenko, O, Arthur, Cp, Brown, V, Burhan, H, Chaudhuri, R, Collier, D, Barnes, Nc, Davies, Ej, Ellery, A, Kwok, S, Lenney, W, Nordstrom, M, Pandya, Hc, Parker, Iw, Rajakulasingam, K, Seddon, P, Sharma, R, Thomas, Ec, Wakeling, Ja, Abalos-Galito, M, Abboy, C, Abreu, E, Ackerman, If, Acosta, Ia, Adaoag, Aa, Ahmed, M, Ali, Mi, Allen, Dr, Allen GG Jr, Diogo, Jj, Allison, Dc, Alwine, Lk, Apaliski, Sj, Arastu, Rs, Arora, Cm, Auerbach, D, Azzam, Sj, Badar FL 3rd, Baker, Jw, Barasch, Jp, Barber, Ma, Bardinas-Rodriguez, R, Barreiro, Tj, Baumbach, Rr, Baur, Ce, Baxter, Bs, Beach, Jl, Beasley, Rl, Beavins, Je, Beliveau, Wj, Benbow, Mj, Bennett, Nl, Bennett, Rl, Bernal, H, Bernstein, Di, Blaiss, Ms, Blumenthal, Kw, Boas, Sr, Borders, Jl, Boscia, Ja, Boulware, Wn, Bowling, Bt, Brabec, Ba, Bramlet, Dg, Figueroa, Dp, Brautigam, Df, Brownell, Jm, Bruce, Tr, Call, Rs, Campbell, Ca, Canaan, Ya, Cannon, Df, Carpio, Jm, Cathcart, Ws, Cevallos, Jp, Chauhan, Av, Chuang, Rb, Chevalier, D, Christensen, J, Christensen, Ta, Christina, Mo, Chrzanowski, Rr, Civitarese, Fa, Clark, Jp, Clifford, Dp, Lapidus, Rj, Coggi, Ja, Lenz, Jj, Cohen, Kr, Collins, Bg, Collins, H, Comellas, A, Condit, J, Cordasco EM Jr, Corder, Cn, Covar, Ra, Coverston, Kd, Croce, Sa, Cruz, H, Curtis, Ct, Daftary, Pk, Dalan, D, Dalawari, Sp, Daly, Wc, Davis, Kc, Dawes, Kw, Decotiis, Ba, Deluca, Rf, Desantis, Dm, De Valle OL, Diaz, Jl, Diaz, Jd, Dice, Jp, Elizalde, A, Hosler, Mr, Dixon, C, Dobkin, La, Dobrusin, Rs, Dransfield, Mt, Ebbeling, Wl, Edwards, Jd, Elacion, Jm, Elkayam, D, Ellison, Wt, Elsen, Jr, Engel, Lr, Ensz, Dj, Ericksen, Cl, Ervin, Je, Fang, C, Abrahamian, F, Farrah, Vb, Field, Jd, Fishman, Hj, Florea, R, Nayyar, S, Focil, A, Focauld, F, Franco MA Jr, Frandsen, Br, Ganti, K, Garcia, Fl, Lee, Wm, Garscadden, Ag, Gatti, Ea, Gellady, Am, George, Ar, Gibbon, Gw, Gleason, Gp, Goldberg, P, Goldstein, Mf, Gonzalez, Ge, Gower, Rg, Grande, Ja, Gregory, D, Grubb, Sd, Guthrie, Rp, Haas, Ta, Haft, Ks, Hajal, R, Hammond, Gd, Hansel, Nn, Hansen, Vr, Harris, Af, Hartman, An, Harvey, Rr, Hazan-Steinberg, S, Headley, Dm, Heigerick, Gc, Heller, Bn, Hendrix, El, Herrod, Jn, Hewitt, Mj, Hines, Rl, Hirdt, Ap, Hirschfield, Ja, Hoffman, Ks, Hogan, Ad, Howland, Wc, Hsu, Cc, Hsu, Fj, Hubbard, Wm, Hudson, Jd, Huffman, C, Hussain, M, Ioachimescu, Oc, Ismail, Ym, Jaffrani, Na, Jiang, N, Jones, Sw, Jordan, Rs, Joshi, Ke, Kaashmiri, Mw, Kalafer, M, Kamdar, Ba, Kanuga, Jg, Kao, Nl, Karetzky, M, Katsetos, Jc, Kay, Js, Kimmel, Ma, Kimura, Sh, Kingsley, Jk, Mahmood, Sm, Subich, Dc, Kirstein, Jl, Kleerup, Ec, Klein, Rm, Koh, Dw, Kohli, N, Koura, Fa, Kovacs, Sp, Kratzer, J, Kreit, Ci, Kreutter, Fm, Kubicki, Tm, Labuda, Jm, Latorre, Aj, Lara, Mm, Lechin, Ae, Lee, Jj, Lee, Md, Lentnek, Al, Lesh, Kw, Levins, Pf, Anspach, Rb, Levinsky, Dm, Lillestol, Mj, Lim, H, Livezey, Md, Lloyd-Turney, Cw, Lockey, Rf, Long, Ra, Lynch, Mj, Macgillivray, Bk, Mahadevan, Kp, Makam, Sk, Maloney, Mj, Mapel, D, Margolis, Bd, Margulies, J, Martin, Ef, Martin, Ee, Mascolo, M, Mataria, H, Sunbuli, M, Mathur, Rn, Mattar, Pn, Maynard, Km, Maynard, N, Mccormick, B, Mcelya, M, Mcevoy, Ce, Mckenzie, Wc, Medwedeff, Le, Mehta, Kd, Melamed, Ir, Meli, Jv, Merrick, Bh, Meyers, Pj, Miller, Bt, Minton, Sm, Miranda, Fg, Mohar, De, Montenegro, Ch, Morris, Fa, Morrison, Bs, Moss, Mh, Munoz, F, Naini, Gr, Nakamura, Ct, Naseeruddin, S, Nassim, C, Navazo, Lj, Nissim, Je, Norman, D, Oberoi, Ms, O'Connor, Tm, Offenberger, J, Orr, Rr, Osea, Ea, Paine, Wj, Rasmussen, Nl, Palatnik, M, Pangtay, D, Panuto, Ja, Patel, M, Perera, Ms, Perez, A, Peters PH Jr, Pimentel SM Jr, Pluto, Tm, Pollock, Mt, Posner, Ls, Pritchard, Jc, Pudi, Kk, Puig, Cm, Qaqundah, Py, Radbill, Mk, Rahman, St, Raikhel, M, Raissy, Hh, Ramstad, Ds, Ranasinghe, Es, Rangel, Os, Rapo, Se, Raschal, Sp, Reddy, Dg, Rehman, Sm, Reyes, Sr, Rhodes, Rb, Riffer, E, Rihal, Ps, Riley ED 4th, Rodriguez, Dh, Rogers, Cm, Rohlf, Jl, Romeu, H, Roney, Cw, Ronsick, So, Rosen, Jb, Rowe, Ms, Ruoff, Ge, Ryan, Eh, Saff, Rh, Saini, N, Anand, S, Balakrishnan, K, Samuels, Bs, Samuelson, Rj, Saniuk, Rj, Sargeant, Wo, Saunders, Mk, Saway, W, Scarupa, Md, White, Mv, Schear, Mj, Schwarz, Cm, Scott, Rb, Segall, N, Seibert, Af, Seidmeyer, V, Seidner, Mr, Seifer, Fd, Serje, J, Shah, Ms, Shah, Sb, Shapero, Pa, Shearer, Sd, Sheikh, Sq, Shepherd, Ts, Sher, Er, Sher, Ld, Short, Bh, Silas, Pe, Alvey, Jc, Silverfield, Jc, Simon, Sj, Sitar, S, Skoner, Dp, Smallow, Sa, Smart, Ba, Smith, Ca, Smith, Ke, Smith, Sk, Snyders, Gc, Soong, W, Soufer, J, Spangenthal, S, Stahlman, Je, Steele, Lg, Stegemoller, Rk, Stocks, J, Storms, Ww, Suen, J, Surowitz, Rz, Swauger, Jr, Taber, La, Tan, Ae, Pratt, Se, Tanus, T, Tarpay, Mm, Tarshis, Ga, Tenney, Jw, Tilghman, Kg, Trevino, Me, Troyan, Be, Twiddy, Sk, Updegrove, Jd, Urval, Kr, Uusinarkaus, Kt, Vaela, R, Van Cleeff, M, Varano, S, Vo, Qd, Wainz, Rj, Wald, Ja, Wall, Sj, Wasserman, Rl, Weinstein, Dl, Welker, Ja, Wellmon, B 2nd, Wells, T, Wenocur, Hs, Williams, Dl, Williams, Sl, Win, Ph, Wingo, Td, Wisman PP Jr, Wyszomierski, Da, Yamada, Hm, Yarows, S, Yunger TM Jr, Ziering, Rw., the AUSTRI Investigators, Stempel, D., Raphiou, I., Kral, K., Yeakey, A., Emmett, A., Prazma, C., Buaron, K., and Pascoe, S. Scichilone N tra i collaboratori
- Subjects
Male ,asthma ,serious events ,fluticasone ,salmeterol ,AUSTRI ,Exacerbation ,Intention to Treat Analysi ,INHALED CORTICOSTEROIDS ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,immune system diseases ,Ús terapèutic ,Broncodilatadors ,030212 general & internal medicine ,Child ,Fluticasone ,RISK ,ACTING BETA-AGONISTS ,EXACERBATIONS ,METAANALYSIS ,MORTALITY ,SAFETY ,DEATH ,FDA ,Medicine (all) ,Hazard ratio ,General Medicine ,Bronchodilator agents ,Middle Aged ,Fluticasone-Salmeterol Drug Combination ,Bronchodilator Agents ,Intention to Treat Analysis ,Anesthesia ,Female ,Salmeterol ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Settore MED/10 - Malattie Dell'Apparato Respiratorio ,Fluticasone propionate ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Administration, Inhalation ,medicine ,Humans ,Asma ,Bronchodilator Agent ,Asthma ,Aged ,Proportional Hazards Models ,business.industry ,Therapeutic use ,medicine.disease ,respiratory tract diseases ,030228 respiratory system ,Fluticasone Propionate, Salmeterol Xinafoate Drug Combination ,Proportional Hazards Model ,business - Abstract
BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone–salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone–salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone–salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone–salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone–salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P
- Published
- 2016
9. The re-emerging burden of rickets: a decade of experience from Sydney.
- Author
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Robinson PD, Högler W, Craig ME, Verge CF, Walker JL, Piper AC, Woodhead HJ, Cowell CT, and Ambler GR
- Abstract
AIM: To define the demographics and clinical characteristics of cases presenting with nutritional rickets to paediatric centres in Sydney, Australia. METHODS: Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x ray changes. RESULTS: A steady increase was seen in the number of cases per year, with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1 months, with 25% presenting at less than 6 months of age. The most common presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males presented at a younger age, with a lower weight SDS, and more often with seizures. The caseload was almost exclusively from recently immigrated children or first generation offspring of immigrant parents, with the region of origin predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS: This large case series shows that a significant and increasing caseload of vitamin D deficiency remains, even in a developed country with high sunlight hours. Cases mirror recent immigration trends. Since birth or residence in Australia does not appear to be protective, screening of at risk immigrant families should be implemented through public health policies. [ABSTRACT FROM AUTHOR]
- Published
- 2006
10. Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.
- Author
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Patel P, Robinson PD, Fisher BT, Phillips R, Morgan JE, Lehrnbecher T, Kuczynski S, Koenig C, Haeusler GM, Esbenshade A, Elgarten C, Duong N, Diorio C, Castagnola E, Beauchemin MP, Ammann RA, Dupuis LL, and Sung L
- Abstract
Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI., Competing Interests: BTF has served on a data safety monitoring board for Astellas and BTF's institution has received grant support from Allovir and Pfizer as well as CDC, FDA and NIH for research performed. CD has received support from Abramson Cancer Center K12 and a CIHR Fellowship Award. TL's institution has received an unrestricted research grant by Gilead Sciences and TL has received payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from: Astra Zeneca, EUSA Pharma, Gilead Sciences, MSD/Merck and Pfizer. TL has received support for attending meetings and/or travel from EUSA Pharma and has served on a data safety monitoring board or advisory board for: EUSA Pharma, Gilead Sciences, Merck/MSD, Mundipharma, Pfizer and Pharming. TL has had a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid at: Working Party Infection German Society of Pediatric Oncology and Hematology and Working Party Infection German Society of Pediatric Infectious Diseases. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2024 The Author(s).)
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- 2024
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11. Nationwide lung function monitoring from infancy in newborn-screened children with cystic fibrosis.
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Sandvik RM, Schmidt MN, Voldby CM, Buchvald FF, Olesen HV, Olsen J, Kragh MV, Rubak SLM, Pressler T, Robinson PD, Gustafsson PM, Skov M, and Nielsen KG
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Background: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor., Methods: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study., Results: 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment., Conclusions: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory., Competing Interests: Conflict of interest: None of the authors have personal financial relationships with any organisations that might have an interest in the submitted work., (Copyright ©The authors 2023.)
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- 2023
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12. Guideline for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients: 2023 update.
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Patel P, Robinson PD, van der Torre P, Tomlinson D, Seelisch J, Oberoi S, Morgan JE, Hinds PS, Götte M, Gibson F, Duong N, Davis H, Culos-Reed SN, Cataudella D, Miranda V, Dupuis LL, and Sung L
- Abstract
Objective was to update a clinical practice guideline (CPG) for the management of fatigue in children and adolescents with cancer or pediatric hematopoietic cell transplant recipients. We reconvened a multi-disciplinary and multi-national panel. While the previous 2018 CPG evaluated adult and pediatric randomized controlled trials (RCTs) to manage fatigue, this 2023 update revised previous recommendations based only on pediatric RCTs. Twenty RCTs were included in the updated systematic review. Physical activity significantly reduced fatigue (standardized mean difference -0.44, 95% confidence interval -0.64 to -0.24; n = 8 RCTs). Using the 2018 recommendations as a basis, the panel continued to make strong recommendations to use physical activity, and to offer relaxation, mindfulness or both, to manage fatigue in pediatric patients. Cognitive or cognitive behavioral therapies may be offered. Pharmacological approaches should not be routinely used. The panel made a new good practice statement to routinely assess for fatigue, ideally using a validated scale., Competing Interests: PSH received grants or research support from NIH; royalties or licenses from Lippincott; consulting fees from MSKCC and participated on the REACH Board at Nemours, Delaware. SNCR received grants from CIHR, CCS and Kids Cancer Care-IMPACT. LS is supported by the Canada Research Chair in Pediatric Oncology Supportive Care. No other authors declared a conflict of interest., (© 2023 The Author(s).)
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- 2023
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13. Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?
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Warner S, Blaxland A, Counoupas C, Verstraete J, Zampoli M, Marais BJ, Fitzgerald DA, Robinson PD, and Triccas JA
- Abstract
Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4
+ T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4+ T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus . This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4+ T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.- Published
- 2023
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14. Multiple breath washout and oscillometry after allogenic HSCT: a scoping review.
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Sonneveld N, Rayment JH, Usemann J, Nielsen KG, and Robinson PD
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- Humans, Oscillometry, Respiratory Function Tests, Spirometry, Lung, Hematopoietic Stem Cell Transplantation adverse effects
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Pulmonary chronic graft- versus -host disease (cGVHD) is a substantial cause of pulmonary morbidity and mortality post-haematopoietic stem cell transplantation (HSCT). Current spirometry-based monitoring strategies have significant limitations. Understanding the utility of novel peripheral airway function tests - multiple breath washout (MBW) and oscillometry - is critical in efforts to improve detection, facilitate earlier intervention and improve outcomes. In this scoping review, we identified 17 studies investigating MBW or oscillometry, or both, after allogenic HSCT. Despite small study numbers limiting the ability to draw firm conclusions, several themes were evident. Detectable peripheral airway abnormality in MBW occurred in a substantial proportion prior to HSCT. MBW indices post-HSCT were more frequently abnormal than spirometry when reporting group data and among those with extrapulmonary cGVHD and pulmonary cGVHD. Changes in MBW indices over time may be more indicative of pulmonary complications than absolute values at any given time point. Oscillometry indices were often normal at baseline, but more frequently abnormal in those who developed pulmonary cGVHD. Pooling currently available individual participant data across these studies may improve our ability to formally compare their respective sensitivity and specificity at specific time points and assess the trajectory of MBW and oscillometry indices over time., Competing Interests: Conflict of interest: N. Sonneveld has nothing to disclose. Conflict of interest: J.H. Rayment has nothing to disclose. Conflict of interest: J. Usemann has nothing to disclose. Conflict of interest: K.G. Nielsen has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose., (Copyright ©The authors 2023.)
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- 2023
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15. Utilising Hem-o-lok ® ligation system to safely and efficiently divide bilioenteric fistulae in laparoscopic cholecystectomy.
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Finch LM, Robinson PD, and Szentpali K
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- Humans, Ligation, Surgical Instruments, Cholecystectomy, Laparoscopic adverse effects, Laparoscopy
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- 2023
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16. Assessing the calculation of conductive and acinar ventilatory heterogeneity indices S cond and S acin from multiple-breath washout data.
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Prisk GK, Rutting S, Bozier J, Thamrin C, Robinson PD, and Thompson BR
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- Adult, Humans, Respiratory Function Tests methods, Functional Residual Capacity, Breath Tests methods, Lung, Respiration
- Abstract
Sensor errors resulting in elevated values of N
2 concentration [N2 ] in commercial multiple-breath washout (MBW) devices have been shown to prolong the washout and result in erroneously high functional residual capacity (FRC) and lung clearance index (LCI) values. The errors also affect the indices of conductive and acinar ventilatory heterogeneity ( Scond and Sacin ) although the mechanism by which this change in values occurs remains unclear. Exploring these effects also provides a timely opportunity to examine the appropriateness of the algorithm used to calculate these indices. Using a two-compartment model with differing specific ventilation (SV) such that the lower SV unit empties late, noise-free MBW were simulated both corrected and uncorrected for the recent sensor error. Scond was calculated using regression of normalized phase III slope (SnIII ) against lung turnover (TO) from a TO range starting at 1.5 and ending at an upper turnover (TOupper ) between 4 and 8 (default 6) over a range of simulated values. The principal effect of the sensor error was that as the MBW proceeded the phase III slope of successive breaths was normalized by an increasingly overestimated [N2 ], resulting in SnIII values that fell precipitously at high TO, greatly reducing Scond . Reanalysis of previously published data and of simulated data showed a large proportional bias in Scond , whereas Sacin was only minimally affected. In adult subject data, reducing TOupper below 5.5 was associated with a large drop of up to ∼60% in Scond calculated from data corrected for sensor error. Raising the upper TO limit elevated Scond by ∼20% but with a large concomitant increase in variability. In contrast to Scond , Sacin was relatively unaffected by changes in TOupper with changes of <3%. This work serves to emphasize that the upper limit of TO of 6 represents an appropriate upper limit for the calculation of Scond . NEW & NOTEWORTHY Sensor errors that elevated values of N2 concentration in commercial multiple-breath washout (MBW) devices resulted in errors in calculated parameters including Scond and Sacin . We examined the mechanism of the change in values produced by these errors and explored the appropriateness of the calculation of Scond and Sacin . This work serves to emphasize that the current algorithm in use is appropriate for the calculation of Scond and Sacin .- Published
- 2023
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17. UnloCKing the Role of Creatine Kinase in Childhood Asthma.
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Forno E and Robinson PD
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- Humans, Creatine Kinase, Asthma
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- 2023
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18. Patterns of Change in the Severity of Airway Obstruction with Robin Sequence in Early Infancy.
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Dede BD, Robinson PD, Castro C, and Waters KA
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Previous studies suggest that infants with Robin sequence show a pattern of steady improvement in the severity of airway obstruction, and of their treatment requirements, during infancy., Methods: Three infants with Robin sequence and severe obstructive sleep apnea were managed with nasal continuous positive airways pressure (CPAP). Multiple measures of airway obstruction were made during infancy, including CPAP pressure evaluations and sleep studies (screening and polysomnography studies). Parameters reported include obstructive apnea-hypopnea index, oxygen desaturation parameters, and CPAP pressures required for effective airway management., Results: CPAP pressure requirements increased in all three infants during their first weeks of life. Apnea indices on polysomnography did not track with the CPAP pressure requirements. Peak pressure requirements were at 5 and 7 weeks for two patients, with subsequent gradual decline and cessation of therapy CPAP at 39 and 74 weeks, respectively. The third patient had a complicated course, jaw distraction at 17 weeks, and biphasic CPAP pressure requirement (first peak at 3 weeks, but maximum pressure at 74 weeks), with cessation of CPAP at 75 weeks., Conclusions: The observed pattern of early increases in CPAP pressure requirements for infants with Robin sequence adds to the complexities of managing this disorder. Factors that may lead to this pattern of change in airway obstruction are discussed., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)
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- 2023
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19. Clinical practice guideline recommendation summaries for pediatric oncology health care professionals: A qualitative study.
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Santesso N, Beauchemin M, Robinson PD, Walsh AM, Sugalski AJ, Lo T, Dang H, Fisher BT, Grimes AC, Wrightson AR, Yu LC, Sung L, and Dupuis LL
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- Child, Humans, Qualitative Research, Medical Oncology, Health Personnel, Neoplasms
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Objective: To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals., Methods: We developed a summary format based on current research and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal., Results: During seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable., Conclusions: A summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Santesso et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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20. The dilemma of improving rational antibiotic use in pediatric community-acquired pneumonia.
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Nguyen PTK, Robinson PD, Fitzgerald DA, and Marais BJ
- Abstract
Pneumonia is the number one cause of disease and deaths in children under five years old, outside the neonatal period, with the greatest number of cases reported from resource-limited settings. The etiology is variable, with not much information on the local etiology drug resistance profile in many countries. Recent studies suggest an increasing contribution from respiratory viruses, also in children with severe pneumonia, with an increased relative contribution in settings that have good vaccine coverage against common bacterial pathogens. Respiratory virus circulation was greatly reduced during highly restrictive measures to contain the spread of COVID-19 but rebounded once COVID-19 restrictions were relaxed. We conducted a comprehensive literature review of the disease burden, pathogens, case management and current available prevention of community acquired childhood pneumonia, with a focus on rational antibiotic use, since the treatment of respiratory infections is the leading cause of antibiotic use in children. Consistent application of revised World Health Organisation (WHO) guidance that children presenting with coryzal symptoms or wheeze can be managed without antibiotics in the absence of fever, will help to reduce unnecessary antibiotic use, as will increased availability and use of bedside inflammatory marker tests, such as C-reactive protein (CRP) in children with respiratory symptoms and fever., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Nguyen, Robinson, Fitzgerald and Marais.)
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- 2023
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21. Turning lung clearance index on its head. Reference data for SF 6 multiple-breath washout derived ventilation distribution efficiency.
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Sandvik RM, Lindblad A, Robinson PD, Nielsen KG, and Gustafsson P
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- Adult, Female, Humans, Child, Male, Respiration, Respiratory Function Tests methods, Tidal Volume, Breath Tests methods, Lung, Cystic Fibrosis
- Abstract
Cystic fibrosis (CF) lung disease is characterized by increased ventilation inhomogeneity (VI), as measured by multiple-breath washout (MBW). Lung clearance index (LCI) is the most reported VI outcome. This study aimed to evaluate historically published reference equations for sulfur hexafluoride (SF
6 ) MBW outcomes, to data collected using updated commercial SF6 MBW equipment, and to produce device-specific equations if necessary. SF6 MBW was performed in 327 healthy children aged 0.1-18.4 yr [151 (46%) girls], 191 (58.4%) <3 yr. z-Scores were calculated from published reference equations (FRC and LCI) and multivariate linear regression was performed to produce device-specific reference equations. Due to increasing residual standard deviations with increasing LCI values, investigation of methods for improvement were investigated, based on the relationship between VI and dead space ventilation (VD/VT; dead space volume/tidal volume) in a cohort of 59 healthy children, 26 children with CF ( n = 138 test occasions), and 49 adults with lung disease. Historical SF6 MBW reference equations were unsuitable for EXHALYZER D data. In contrast to LCI and log10 (LCI), 1/LCI (ventilation distribution efficiency; VDE) was linearly related to VD/VT, with z-scores linearly related to its absolute values. Reference equations were reported for VDE and log10 (FRC). Significant predictors for VDE and log10 (FRC), respectively, were log10 (age) and sex, and log10 (height), sex, and posture. VDE is potentially a better index of VI than LCI, particularly in more advanced CF lung disease and also for longitudinal monitoring. Further confirmatory clinical studies, particularly longitudinal imaging studies of structural or ventilatory changes, are warranted. NEW & NOTEWORTHY Lung clearance index (LCI) is the most used outcome from the multiple-breath washout test. As known for decades, the LCI is not linearly related to dead space ventilation, giving difficulties interpreting changes over time and in clinical trials. We present a new and improved outcome based on LCI, the ventilation distribution efficiency (VDE), which solves this problem by being linearly related to dead space ventilation. A pediatric age range reference equation for VDE is presented.- Published
- 2023
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22. Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation: A Phase 3b, Randomized, Placebo-controlled Study.
- Author
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Mall MA, Brugha R, Gartner S, Legg J, Moeller A, Mondejar-Lopez P, Prais D, Pressler T, Ratjen F, Reix P, Robinson PD, Selvadurai H, Stehling F, Ahluwalia N, Arteaga-Solis E, Bruinsma BG, Jennings M, Moskowitz SM, Noel S, Tian S, Weinstock TG, Wu P, Wainwright CE, and Davies JC
- Subjects
- Child, Humans, Aminophenols adverse effects, Benzodioxoles adverse effects, Chloride Channel Agonists adverse effects, Forced Expiratory Volume, Mutation, Cystic Fibrosis drug therapy, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Cystic Fibrosis Transmembrane Conductance Regulator therapeutic use
- Abstract
Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation ( F /MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA ( n = 60) or placebo ( n = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index
2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F /MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings.- Published
- 2022
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23. Ultrafine particle exposure and biomarkers of effect on small airways in children.
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Robinson PD, Salimi F, Cowie CT, Clifford S, King GG, Thamrin C, Hardaker K, Mazaheri M, Morawska L, Toelle BG, and Marks GB
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- Bayes Theorem, Biomarkers, Child, Cross-Sectional Studies, Female, Humans, Male, Particle Size, Air Pollutants adverse effects, Particulate Matter adverse effects
- Abstract
The small size and large surface area of ultrafine particles (UFP) enhance their ability to deposit in the lung periphery and their reactivity. The Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) cross-sectional study was conducted in 8-11-year-old schoolchildren attending 25 primary (elementary) schools, randomly selected from the Brisbane Metropolitan Area, Queensland, Australia. Main study findings outlined indirect evidence of distal airway deposition (raised C reactive protein) but as yet, there is no direct evidence in the literature of effects of UFP exposure on peripheral airway function. We present further UPTECH study data from two sensitive peripheral airway function tests, Oscillometry and Multiple Breath Nitrogen Washout (MBNW), performed in 577 and 627 children (88% and 96% of UPTECH study cohort) respectively: mean(SD) age 10.1(0.9) years, 46% male, with 50% atopy and 14% current asthma. Bayesian generalised linear mixed effects regression models were used to estimate the effect of UFP particle number count (PNC) exposure on key oscillometry (airway resistance, (Rrs), and reactance, (Xrs)) and MBNW (lung clearance index, (LCI) and functional residual capacity, (FRC)) indices. We adjusted for age, sex, and height, and potential confounders including socio-economic disadvantage, PM
2.5 and NO2 exposure. All models contained an interaction term between UFP PNC exposure and atopy, allowing estimation of the effect of exposure on non-atopic and atopic students. Increasing UFP PNC was associated with greater lung stiffness as evidenced by a decrease in Xrs [mean (95% credible interval) -1.63 (-3.36 to -0.05)%] per 1000#.cm-3 ]. It was also associated with greater lung stiffness (decrease in Xrs) in atopic subjects across all models [mean change ranging from -2.06 to -2.40% per 1000#.cm-3 ]. A paradoxical positive effect was observed for Rrs across all models [mean change ranging from -1.55 to -1.70% per 1000#.cm-3 ] (decreases in Rrs indicating an increase in airway calibre), which was present for both atopic and non-atopic subjects. No effects on MBNW indices were observed. In conclusion, a modest detrimental effect of UFP on peripheral airway function among atopic subjects, as assessed by respiratory system reactance, was observed extending the main UPTECH study findings which reported a positive association with a biomarker for systemic inflammation, C-reactive protein (CRP). Further studies are warranted to explore the pathophysiological mechanisms underlying increased respiratory stiffness, and whether it persists through to adolescence and adulthood., (Copyright © 2022. Published by Elsevier Inc.)- Published
- 2022
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24. The effect of oxygen and carbon dioxide cross-sensitivity sensor error in the Eco Medics Exhalyzer D device on measures of conductive and acinar airway function.
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Bozier J, Jeagal E, Robinson PD, Prisk GK, Chapman DG, King GG, Thamrin C, and Rutting S
- Abstract
Introduction: The multiple breath nitrogen washout (MBNW) test provides important clinical information in obstructive airways diseases. Recently, a significant cross-sensitivity error in the O
2 and CO2 sensors of a widely used commercial MBNW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) was detected, which leads to overestimation of N2 concentrations. Significant errors in functional residual capacity (FRC) and lung clearance index (LCI) have been reported in infants and children. This study investigated the impact in adults, and on additional important indices reflecting conductive ( Scond ) and acinar ( Sacin ) ventilation heterogeneity, in health and disease., Methods: Existing MBNW measurements of 27 healthy volunteers, 20 participants with asthma and 16 smokers were reanalysed using SPIROWARE V 3.3.1, which incorporates an error correction algorithm. Uncorrected and corrected indices were compared using paired t-tests and Bland-Altman plots., Results: Correction of the sensor error significantly lowered FRC (mean difference 9%) and LCI (8-10%) across all three groups. Scond was higher following correction (11%, 14% and 36% in health, asthma and smokers, respectively) with significant proportional bias. Sacin was significantly lower following correction in the asthma and smoker groups, but the effect was small (2-5%) and with no proportional bias., Discussion: The O2 and CO2 cross-sensitivity sensor error significantly overestimated FRC and LCI in adults, consistent with data in infants and children. There was a high degree of underestimation of Scond but minimal impact on Sacin . The presence of significant proportional bias indicates that previous studies will require reanalysis to confirm previous findings and to allow comparability with future studies., Competing Interests: Conflict of interest: No conflicts of interest, financial or otherwise, relating to this study are declared by the authors., (Copyright ©The authors 2022.)- Published
- 2022
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25. Impact of cross-sensitivity error correction on representative nitrogen-based multiple breath washout data from clinical trials.
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Robinson PD, Jensen R, Seeto RA, Stanojevic S, Saunders C, Short C, Davies JC, and Ratjen F
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- Breath Tests, Functional Residual Capacity, Humans, Respiratory Function Tests, Cystic Fibrosis diagnosis, Cystic Fibrosis therapy, Nitrogen
- Abstract
Competing Interests: Declaration of Competing Interest Ms Jensen, Mr Seeto, Dr Stanojevic and Dr Ratjen report other from Vertex Pharmaceuticals and grants (#SHIP14K0) from the CF Foundation during the conduct of the study. Ms Saunders and Mr Short report other from Vertex Pharmaceuticals and ECFS CTN during the conduct of the study. Dr. Robinson reports other from Vertex Pharmaceuticals Ltd during the conduct of the study. Dr. Davies reports other from Algipharma AS, other from Bayer AG, other from Boehringer Ingelheim Pharma GmbH & Co. KG, other from Galapagos NV, other from ImevaX GmbH, other from Nivalis Therapeutics, Inc., other from ProQR Therapeutics III B.V., other from Proteostasis Therapeutics, INC., other from Raptor Pharmaceuticals, Inc, other from Vertex Pharmaceuticals (Europe) Limited, other from Enterprise, other from Novartis, other from Pulmocide, other from Flatley, other from Nivalis Therapeutics Inc., grants from CF Trust, other from Teva, outside the submitted work.
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- 2022
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26. Technical standards for respiratory oscillometry and bronchodilator response cut-offs.
- Author
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Thamrin C, Robinson PD, Farah CS, and King GG
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- Humans, Oscillometry, Respiratory System, Spirometry, Asthma diagnosis, Asthma drug therapy, Bronchodilator Agents therapeutic use
- Abstract
Competing Interests: Conflict of interest: C. Thamrin reports intellectual property arrangements/contracts from Restech SRL, Milan, Italy; equipment on loan for research studies from Restech SRL, Milan, Italy and THORASYS Thoracic Medical Systems, Montreal, Canada; outside the submitted work. G.G. King reports grants, personal fees and other from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Menarini, MundiPharma, grants from National Health and Medical Research Council, Professional Societies, The University of Sydney, and philanthropic individuals and societies, outside the submitted work. All other authors have nothing to disclose.
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- 2022
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27. Clinical significance and applications of oscillometry.
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Kaminsky DA, Simpson SJ, Berger KI, Calverley P, de Melo PL, Dandurand R, Dellacà RL, Farah CS, Farré R, Hall GL, Ioan I, Irvin CG, Kaczka DW, King GG, Kurosawa H, Lombardi E, Maksym GN, Marchal F, Oostveen E, Oppenheimer BW, Robinson PD, van den Berge M, and Thamrin C
- Subjects
- Humans, Oscillometry, Respiratory Function Tests, Spirometry, Airway Resistance, Asthma
- Abstract
Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease., Competing Interests: Conflict of interest: D.A. Kaminsky reports personal payments made as faculty speaker for Cardiorespiratory Diagnostics Seminar from MGC Diagnostics, Inc. outside the submitted work. Past Chair of ATS Proficiency Standards for Pulmonary Function Laboratories Committee, unpaid. Conflict of interest: S.J. Simpson has nothing to disclose. Conflict of interest: K.I. Berger has nothing to disclose. Conflict of interest: P. Calverley reports receiving consulting fees paid by Phillips Respironics for advisory work on a novel COPD ventilator. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Phillips Respironics, outside the submitted work. Conflict of interest: P.L. de Melo reports patent 28727 issued. Conflict of interest: R.J. Dandurand reports grants or contracts paid to the institution from AstraZeneca, Boehringer-Ingelheim, Covis Pharma, Grifols, MGC Diagnostics, Teva Pharma, Thorasys, and Vyaire, outside the submitted work. Speaking payment from Novartis for L'oscillométrie en clinique: qu'ajoute-t-elle aux évaluations pulmonaires?, 18 September 2019, Boehringer-Ingelheim for L'oscillométrie: vieille physiologie avec un avenir brilliant, 17 November 2020, and Latin American Respiratory Physiology Society for Oscillometry in Asthma and COPD: Interpretation Strategies, 14 November 2020, outside the submitted work. Chairman, Oscillometry Harmonisation Study Group, an international committee academic and industry experts working to standardise oscillometry devices, and Chairman, Respiratory Effectiveness Group Technologies Working Group, Cambridge, U.K. (https://www.regresearchnetwork.org). Conflict of interest: R.L. Dellacà reports royalties or licenses from Restech, Philips and Vyaire. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Restech and Philips, outside the submitted work. Support for attending meetings from Philips and Vyaire. Patent issued, owned and licensed from Politecnico di Milano University. Member of the Board of Directors for Restech. Stocks owned for Restech. Free loan of equipment for studies received from Vyaire and Restech. Conflict of interest: C.S. Farah has nothing to disclose. Conflict of interest: R. Farré has nothing to disclose. Conflict of interest: G.L. Hall has nothing to disclose. Conflict of interest: I. Ioan has nothing to disclose. Conflict of interest: C.G. Irvin received consulting fees from Medical Graphics Corporation, outside the submitted work. Conflict of interest: D.W. Kaczka reports support for the present manuscript from University of Iowa. Grants or contracts from Dept of Defence and NIH, outside the submitted work. Consulting fees received from ZOLL Medical, Inc. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from CHEST, ASME, Medical Society of New Zealand, and Johns Hopkins University, outside the submitted work. US patent 10,675,423 B2 (patent on MFOV technique, inventor) and PCT patent pending, patent on MFOV technique pending. Stock or stock options held for OscillaVent, Inc. Loan of ventilator for other projects from ZOLL Medical Inc. Conflict of interest: G.G. King reports grants or contracts from Restech Italy, NHMRC, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Menarini, MundiPharma, Philanthropic individuals and societies, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CycloPharm, GlaxoSmithKline, Menarini, MundiPharma and Novartis, outside the submitted work. Leadership or fiduciary role in other board, society, committee or advocacy group for ERS Technical Standards for Respiratory Oscillometry. Conflict of interest: H. Kurosawa reports receiving a grant from CHEST Co. Ltd. Royalties or licence for CHEST Co. Ltd. Payment or honoraria for lectures received from CHEST Co. Ltd. Nippon, Boehringer Ingelheim, Novartis, and Teijin Pharma, outside the submitted work. Conflict of interest: E. Lombardi reports grants or contracts from Restech and Sanofi, outside the submitted work. Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events received from Angelini, Chiesi, GSK, Novartis and Sanofi, outside the submitted work. Participation on a Data Safety Monitoring Board or Advisory Board for GSK and Novartis. Conflict of interest: G.N. Maksym reports grants or contracts from National Research Council of Canada, Cyclomedica Inc. Australia, and Lung Association of Nova Scotia, outside the submitted work. Accommodation Expenses received from Thorasys, Thoracic Medical Systems Inc. for attending European Society Meeting 2019. Patents planned, issued or pending for Method and system to acquire oscillometry measurements, owned by Thorasys, Thoracic Medical Systems Inc. Stock or stock options held for Thorasys, Thoracic Medical Systems Inc. Conflict of interest: F. Marchal has nothing to disclose. Conflict of interest: E. Oostveen has nothing to disclose. Conflict of interest: B.W. Oppenheimer has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: M. van den Berge reports grants or contracts from GlaxoSmithKline, Novartis, Astra Zeneca, Roche, and Genentech, outside the submitted work. Conflict of interest: C. Thamrin report grants or contracts from Restech SRL and THORASYS Thoracic. Equipment on loan for research studies from Restech SRL and THORASYS Thoracic, outside the submitted work., (Copyright ©The authors 2022.)
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- 2022
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28. A Short extension to multiple breath washout provides additional signal of distal airway disease in people with CF: A pilot study.
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Short C, Semple T, Saunders C, Hughes D, Irving S, Gardener L, Rosenthal M, Robinson PD, and Davies JC
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- Adolescent, Adult, Child, Child, Preschool, Cystic Fibrosis diagnostic imaging, Female, Humans, Male, Pilot Projects, Tomography, X-Ray Computed, Young Adult, Breath Tests methods, Cystic Fibrosis physiopathology, Respiratory Function Tests methods
- Abstract
Background: Adding a slow vital capacity (SVC) to multiple breath washout (MBW) allows quantification of otherwise overlooked signal from under/un-ventilated lung units (UVLU) and may provide a more comprehensive assessment of airway disease than conventional lung clearance index (LCI
2.5 )., Methods: We conducted a pilot study on people undergoing MBW tests: 10 healthy controls (HC) and 43 cystic fibrosis (CF) subjects performed an SVC after the standard end of test. We term the new outcome LCI with Short extension (LCIShX ). We assessed (i) CF/ HC differences, (ii) variability (iii) effect of pulmonary exacerbation (PEx)/treatment and (iv) relationship with CF computed tomography (CFCT) scores., Results: HC/ CF group differences were larger with LCIShX than LCI2.5 (P<0.001). Within the CF group UVLU was highly variable and when abnormal it did not correlate with corresponding LCI2.5 . Signal showed little variability during clinical stability (n = 11 CF; 2 visits; median inter-test variability 2.6% LCIShX, 2.5% LCI2.5 ). PEx signal was significantly greater for LCIShX both for onset and resolution. Both MBW parameters correlated significantly with total lung CT scores and hyperinflation but only LCIShX correlated with mucus plugging., Conclusions: UVLU captured within the LCIShX varies between individuals; the lack of relationship with LCI2.5 demonstrates that new, additional information is being captured. LCIShX repeatability during clinical stability combined with its larger signal around episodes of PEx may lend it superior sensitivity as an outcome measure. Further studies will build on this pilot data to fully establish its utility in monitoring disease status., Competing Interests: Declaration of Competing Interest Christopher Short, Clare Saunders, Dominic Hughes, Samantha Irving, Laura Gardener, Mark Rosenthal and Paul Robinson report no conflicts of interest. Thomas Semple reports speakers fees - Vertex Pharmaceuticals. Research grants – Chiesi Pharmaceuticals. Consultancy fees - Boehringer-Ingelheim and Calyx. Prof. Jane Davies has performed clinical trial leadership roles, educational and/ or advisory activities for the following: Abbvie, Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Eloxx, Enterprise, Galapagos NV, ImevaX GmbH, Ionis, Nivalis Therapeutics, Inc., Novartis, ProQR Therapeutics III B.V., Proteostasis Therapeutics, INC., Pulmocide Raptor Pharmaceuticals, Inc, Vertex Pharmaceuticals., (Copyright © 2021. Published by Elsevier B.V.)- Published
- 2022
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29. Controlled versus free breathing for multiple-breath nitrogen washout in asthma.
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Handley BM, Bozier J, Jeagal E, Rutting S, Schoeffel RE, Robinson PD, King GG, Milne S, and Thamrin C
- Abstract
The lack of comparability in indices of ventilation heterogeneity between free- and controlled-breathing MBNW protocols is confirmed in asthma https://bit.ly/3lmri4A., Competing Interests: Provenance: Submitted article, peer reviewed. Conflicts of interest: B.M. Handley has nothing to disclose. Conflicts of interest: J. Bozier has nothing to disclose. Conflicts of interest: E. Jeagal has nothing to disclose. Conflicts of interest: S. Rutting has nothing to disclose. Conflicts of interest: R.E. Schoeffel has nothing to disclose. Conflicts of interest: P.D. Robinson has nothing to disclose. Conflicts of interest: G.G. King reports fees for consultancy services, conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini, MundiPharma. G.G. King also reports NHMRC research grants and fellowships. Conflicts of interest: S. Milne has nothing to disclose. Conflicts of interest: C. Thamrin reports supply of equipment for an unrelated study from Restech SRL. C. Thamrin also reports funded research collaboration for an unrelated project., (Copyright ©The authors 2021.)
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- 2021
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30. Facilitators and barriers to clinical practice guideline-consistent supportive care at pediatric oncology institutions: a Children's Oncology Group study.
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Sugalski AJ, Lo T, Beauchemin M, Grimes AC, Robinson PD, Walsh AM, Santesso N, Dang H, Fisher BT, Wrightson AR, Yu LC, Sung L, and Dupuis LL
- Abstract
Background: Clinical practice guideline (CPG)-consistent care improves patient outcomes, but CPG implementation is poor. Little is known about CPG implementation in pediatric oncology. This study aimed to understand supportive care CPG implementation facilitators and barriers at pediatric oncology National Cancer Institute (NCI) Community Oncology Research Program (NCORP) institutions., Methods: Healthcare professionals at 26 pediatric, Children's Oncology Group-member, NCORP institutions were invited to participate in face-to-face focus groups. Serial focus groups were held until saturation of ideas was reached. Supportive care CPG implementation facilitators and barriers were solicited using nominal group technique (NGT), and implementation of specific supportive care CPG recommendations was discussed. Notes from each focus group were analyzed using a directed content analysis. The top five themes arising from an analysis of NGT items were identified, first from each focus group and then across all focus groups., Results: Saturation of ideas was reached after seven focus groups involving 35 participants from 18 institutions. The top five facilitators of CPG implementation identified across all focus groups were organizational factors including charging teams with CPG implementation, individual factors including willingness to standardize care, user needs and values including mentorship, system factors including implementation structure, and implementation strategies including a basis in science. The top five barriers of CPG implementation identified were organizational factors including tolerance for inconsistencies, individual factors including lack of trust, system factors including administrative hurdles, user needs and values including lack of inclusivity, and professional including knowledge gaps., Conclusions: Healthcare professionals at pediatric NCORP institutions believe that organizational factors are the most important determinants of supportive care CPG implementation. They believe that CPG-consistent supportive care is most likely to be delivered in organizations that prioritize evidence-based care, provide structure and resources to implement CPGs, and eliminate implementation barriers., Trial Registration: ClinicalTrials.gov Identifier: NCT02847130. Date of registration: July 28, 2016., (© 2021. The Author(s).)
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- 2021
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31. Update in Pediatrics 2020.
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Forno E, Abman SH, Singh J, Robbins ME, Selvadurai H, Schumacker PT, and Robinson PD
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- Adolescent, Air Pollution, Asthma, Bronchopulmonary Dysplasia, Child, Child, Preschool, Ciliary Motility Disorders, Cystic Fibrosis, Humans, Infant, Infant, Newborn, Infant, Premature, Obesity, Respiratory Distress Syndrome, Newborn, Respiratory Tract Infections, Vaping, Pediatrics, Pulmonary Medicine
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- 2021
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32. Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age.
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Martins Costa Gomes G, de Gouveia Belinelo P, Starkey MR, Murphy VE, Hansbro PM, Sly PD, Robinson PD, Karmaus W, Gibson PG, Mattes J, and Collison AM
- Abstract
Objective: Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10-fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy., Methods: Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t-distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep., Results: Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty-four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor-homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age.", Conclusion: Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
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- 2021
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33. Exposure to Stress and Air Pollution from Bushfires during Pregnancy: Could Epigenetic Changes Explain Effects on the Offspring?
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Murphy VE, Karmaus W, Mattes J, Brew BK, Collison A, Holliday E, Jensen ME, Morgan GG, Zosky GR, McDonald VM, Jegasothy E, Robinson PD, and Gibson PG
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- Child, Child, Preschool, Environmental Exposure adverse effects, Epigenesis, Genetic, Female, Humans, Pregnancy, Smoke adverse effects, Smoke analysis, Air Pollutants analysis, Air Pollutants toxicity, Air Pollution adverse effects, Fires
- Abstract
Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.
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- 2021
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34. Improved agreement between N 2 and SF 6 multiple-breath washout in healthy infants and toddlers with improved EXHALYZER D sensor performance.
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Sandvik RM, Gustafsson PM, Lindblad A, Robinson PD, and Nielsen KG
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- Breath Tests, Child, Preschool, Functional Residual Capacity, Humans, Infant, Respiratory Function Tests, Sulfur Hexafluoride, Lung, Nitrogen
- Abstract
Recent studies indicate limited utility of nitrogen multiple-breath washout (N
2 MBW) in infancy and advocate for using sulfur hexafluoride (SF6 ) MBW in this age-group. Modern N2 MBW systems, such as EXHALYZER D (ECO MEDICS AG, Duernten, Switzerland), use O2 and CO2 sensors to calculate N2 concentrations (in principle, N2 % = 100 - CO2 % - O2 %). High O2 and CO2 concentrations have now been shown to significantly suppress signal output from the other sensor, raising apparent N2 concentrations. We examined whether improved EXHALYZER D N2 signal, accomplished after thorough examination of this CO2 and O2 interaction on gas sensors and its correction, leads to better agreement between N2 MBW and SF6 MBW in healthy infants and toddlers. Within the same session, 52 healthy children aged 1-36 mo [mean = 1.30 (SD = 0.72) yr] completed SF6 MBW and N2 MBW recordings (EXHALYZER D, SPIROWARE version 3.2.1) during supine quiet sleep. SF6 and N2 SPIROWARE files were reanalyzed offline with in-house software using identical algorithms as in SPIROWARE with or without application of the new correction factors for N2 MBW provided by ECO MEDICS AG. Applying the improved N2 signal significantly reduced mean [95% confidence interval (CI)] differences between N2 MBW and SF6 MBW recorded functional residual capacity (FRC) and lung clearance index (LCI): for FRC, from 26.1 (21.0, 31.2) mL, P < 0.0001, to 1.18 (-2.3, 4.5) mL, P = 0.5, and for LCI, from 1.86 (1.68, 2.02), P < 0.001, to 0.44 (0.33, 0.55), P < 0.001. Correction of N2 signal for CO2 and O2 interactions on gas sensors resulted in markedly closer agreement between N2 MBW and SF6 MBW outcomes in healthy infants and toddlers. NEW & NOTEWORTHY Modern nitrogen multiple-breath washout (N2 MBW) systems such as EXHALYZER D use O2 and CO2 sensors to calculate N2 concentrations. New corrections for interactions between high O2 and CO2 concentrations on the gas sensors now provide accurate N2 signals. The correct N2 signal led to much improved agreement between N2 MBW and sulfur hexafluoride (SF6 ) MBW functional residual capacity (FRC) and lung clearance index (LCI) in 52 sleeping healthy infants and toddlers, suggesting a role for N2 MBW in this age-group.- Published
- 2021
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35. Further considerations on normative data for multiple breath washout outcomes.
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Bayfield KJ, Shaar A, and Robinson PD
- Subjects
- Functional Residual Capacity, Humans, Nitrogen, Respiratory Function Tests, Breath Tests, Lung
- Abstract
Competing Interests: Conflict of interest: K.J. Bayfield has nothing to disclose. Conflict of interest: A. Shaar has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose.
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- 2021
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36. Reply: Fixed breathing protocols in multiple-breath-washout testing: truly an option in children?
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Verbanck S, Schuermans D, Paiva M, Robinson PD, and Vanderhelst E
- Subjects
- Child, Humans, Respiratory Function Tests, Respiration
- Abstract
Competing Interests: Conflicts of interest: S. Verbanck has nothing to disclose. Conflicts of interest: D. Schuermans has nothing to disclose. Conflicts of interest: M. Paiva has nothing to disclose. Conflicts of interest: P.D. Robinson has nothing to disclose. Conflicts of interest: E. Vanderhelst has nothing to disclose.
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- 2021
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37. Mitigating increased variability of multiple breath washout indices due to tidal breathing.
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Verbanck S, Schuermans D, Paiva M, Robinson PD, and Vanderhelst E
- Subjects
- Humans, Respiratory Function Tests, Tidal Volume, Respiration
- Abstract
Competing Interests: Conflict of interest: D. Schuermans has nothing to disclose. Conflict of interest: M. Paiva has nothing to disclose. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: E. Vanderhelst has nothing to disclose. Conflict of interest: S. Verbanck has nothing to disclose.
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- 2021
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38. Controlled versus free breathing for multiple breath nitrogen washout in healthy adults.
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Handley BM, Jeagal E, Schoeffel RE, Badal T, Chapman DG, Farrow CE, King GG, Robinson PD, Milne S, and Thamrin C
- Abstract
Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: "controlled breathing", with targeted tidal volume ( V
T ) and respiratory rate (RR); and "free breathing", with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity (FRC), lung clearance index (LCI), Scond , Sacin ) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently proposed correction for VT to Scond and Sacin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17 (0.98) versus 3.18 (0.94) L, p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for Scond (r=0.18, p=0.36) and significant bias for Sacin (0.057 (0.021) L-1 versus 0.085 (0.038) L-1 , p=0.0004). Between-protocol differences in Sacin were related to differences in the breathing pattern, i.e. VT (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but Scond and Sacin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that Scond and Sacin from free breathing, despite VT correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of Scond during free breathing may limit its clinical utility., Competing Interests: Conflict of interest: B.M. Handley has nothing to disclose. Conflict of interest: E. Jeagal has nothing to disclose. Conflict of interest: R.E. Schoeffel has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: C.E. Farrow has nothing to disclose. Conflict of interest: G.G. King reports fees for consultancy services (which include lectures and advisory board services), conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants and fellowships from the National Health & Medical Research Council and the Asthma Foundation, outside the submitted work. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: S. Milne reports personal fees from Novartis and Boehringer Ingelheim outside the submitted work, and is supported by the MITACS Accelerate programme. Conflict of interest: C. Thamrin has nothing to disclose., (Copyright ©ERS 2021.)- Published
- 2021
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39. End-expiratory lung volume remains stable during N 2 MBW in healthy sleeping infants.
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Gustafsson PM, Kadar L, Kjellberg S, Andersson L, Lindblad A, and Robinson PD
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- Cardiac Output, Female, Humans, Infant, Lung Volume Measurements methods, Male, Noble Gases, Oxygen Consumption, Plethysmography methods, Pulmonary Ventilation, Sleep
- Abstract
We have previously shown that functional residual capacity (FRC) and lung clearance index were significantly greater in sleeping healthy infants when measured by N
2 (nitrogen) washout using 100% O2 (oxygen) versus 4% SF6 (sulfur hexafluoride) washout using air. Following 100% O2 exposure, tidal volumes decreased by over 30%, while end-expiratory lung volume (EELV, i.e., FRC) rose markedly based on ultrasonic flow meter assessments. In the present study to investigate the mechanism behind the observed changes, N2 MBW was performed in 10 separate healthy full-term spontaneously sleeping infants, mean (range) 26 (18-31) weeks, with simultaneous EELV monitoring (respiratory inductance plethysmography, RIP) and oxygen uptake (V´O2 ) assessment during prephase air breathing, during N2 washout by exposure to 100% O2 , and subsequently during air breathing. While flow meter signals suggested a rise in ELLV by mean (SD) 26 (9) ml over the washout period, RIP signals demonstrated no EELV change. V'O2 /FRC ratio during air breathing was mean (SD) 0.43 (0.08)/min, approximately seven times higher than that calculated from adult data. We propose that our previously reported flow meter-based overestimation of EELV was in fact a physiological artifact caused by rapid and marked movement of O2 across the alveolar capillary membrane into the blood and tissue during 100% O2 exposure, without concomitant transfer of N2 to the same degree in the opposite direction. This may be driven by the high observed O2 consumption and resulting cardiac output encountered in infancy. Furthermore, the low resting lung volume in infancy may make this error in lung volume determination by N2 washout relatively large., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)- Published
- 2020
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40. Integrating the multiple breath washout test into international multicentre trials.
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Saunders C, Jensen R, Robinson PD, Stanojevic S, Klingel M, Short C, Davies JC, and Ratjen F
- Subjects
- Certification, Data Collection standards, Feasibility Studies, Female, Humans, International Cooperation, Male, Quality Control, Reference Standards, Breath Tests methods, Cystic Fibrosis diagnosis, Cystic Fibrosis drug therapy, Cystic Fibrosis physiopathology, Mucociliary Clearance drug effects, Outcome Assessment, Health Care methods, Respiratory Function Tests methods, Respiratory Function Tests standards, Staff Development methods, Staff Development standards
- Abstract
Background: The lung clearance index (LCI), derived from the Multiple Breath Washout (MBW) test, is sensitive to treatment effects and compared with spirometry has higher feasibility in younger children and requires smaller sample sizes. As a result, the LCI has been endorsed by the European CF Society Clinical Trials Network for use as a primary outcome measure in CF clinical trials., Methods: Here we describe the implementation of standardised protocols for MBW test performance, data collection and quality control to successfully incorporate LCI as a novel outcome measure in a large multicentre phase III clinical trial., Results: Three regional (North America (NA), Europe (EU), Australia (AUS)) central over-reading centres (CORC) were established to provide a collaborative platform for MBW training, certification and quality control of data. One hundred and thirty-two naïve operators from 53 sites across NA, EU and AUS were successfully trained and certified to perform MBW testing. Incorporation of a re-screening opportunity in the study protocol resulted a final screening feasibility rate of 93%, success remained high throughout the study resulting in an overall feasibility of MBW study data of 88.1% (1107/1257). MBW test acceptability was similar between geographical regions: NA (88%), EU (89%) and AUS (89%)., Conclusion: With this approach we achieved high MBW test feasibility and sustained collection of good quality data, demonstrating the utility of LCI as an effective primary endpoint in the first international phase III clinical trial to report LCI as the primary outcome., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2020
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41. Clinical and lung function outcomes in a cohort of children with severe asthma.
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de Gouveia Belinelo P, Nielsen A, Goddard B, Platt L, Da Silva Sena CR, Robinson PD, Whitehead B, Hilton J, Gulliver T, Roddick L, Pearce K, Murphy VE, Gibson PG, Collison A, and Mattes J
- Subjects
- Administration, Inhalation, Adolescent, Asthma drug therapy, Asthma nursing, Australia, Bronchodilator Agents therapeutic use, Child, Child, Preschool, Female, Humans, Male, Respiratory Function Tests, Retrospective Studies, Spirometry, Treatment Outcome, Asthma physiopathology, Lung physiopathology, Outpatient Clinics, Hospital, Practice Patterns, Nurses'
- Abstract
Background: Uncontrolled severe asthma in children is burdensome and challenging to manage. This study aims to describe outcomes in children with uncontrolled severe asthma managed in a nurse-led severe asthma clinic (SAC)., Methods: This retrospective analysis uses data collected from children referred by a paediatric respiratory specialist to a nurse-led SAC for uncontrolled severe asthma between 2014 and 2019. The pre-clinical assessments included a home visit to assess modifiable factors that could be addressed to improve control. A comprehensive lung function analysis was conducted at each visit. Interventions were personalised and included biologic agents. Statistical analysis was performed using nonparametric, two-tailed Mann-Whitney U-test, the parametric Student's t-test, or analysis of variance (ANOVA) as appropriate., Results: Twenty-three children with a median age of 12 years were seen once, and 16 were followed up. Compared to a non-asthmatic (NA) and asthmatic (A) age-matched cohort, children with severe asthma (SA) had a lower FEV1, and FVC% predicted before and after bronchodilator inhalation, and a higher mean Lung Clearance Index [LCI] (10.5 [SA] versus 7.3 [NA] versus 7.6 [A], p = 0.003). Almost 80% of children with SA had an abnormal LCI, and 48% had a reduced FEV1% at the first SAC visit. Asthma control and FEV1% predicted significantly improved at a follow-up visit, while LCI remained abnormal in the majority of children (83%)., Conclusion: Over time, many children with severe asthma showed improved clinical outcomes and lung function while lung ventilation inhomogeneities persisted. Future appropriately controlled studies are required to determine if a nurse-led multidisciplinary SAC is associated with better outcomes.
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- 2020
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42. Effect of change of body position in spontaneous sleeping healthy infants on SF 6 -based multiple breath washout.
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Robinson PD, Kadar L, Lindblad A, and Gustafsson PM
- Subjects
- Female, Functional Residual Capacity, Healthy Volunteers, Humans, Infant, Male, Sulfur Hexafluoride, Lung physiology, Posture, Respiration, Respiratory Function Tests, Sleep
- Abstract
Competing Interests: Conflict of interest: P.D. Robinson has nothing to declare. Conflict of interest: L. Kadar has nothing to declare. Conflict of interest: A. Lindblad has nothing to declare. Conflict of interest: P.M. Gustafsson has nothing to declare.
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- 2019
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43. Optimizing symptom control in children and adolescents with cancer.
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Dupuis LL, Cook S, Robinson PD, Tomlinson D, Vettese E, and Sung L
- Subjects
- Adolescent, Child, Humans, Narration, Neoplasms physiopathology
- Abstract
There is growing recognition of the degree to which symptoms negatively impact on children receiving cancer treatments. A recent study described that almost all inpatient pediatric oncology patients are experiencing at least one bothersome symptom and almost 60% are experiencing at least one severely bothersome symptom. Poor symptom control occurs because of challenges with communication of bothersome symptoms to clinicians, lack of clinical practice guidelines (CPGs) for most of these symptoms, and failure to administer preventative and therapeutic interventions known to be effective for symptom control. This article reviews approaches used to improve symptom control for children receiving cancer treatments. Areas addressed include systematic symptom screening and creation of CPGs for symptom management. Challenges with electronic health integration are also addressed. Several multi-symptom assessment scales have been developed but none have yet been used to directly influence patient management. The number of CPGs applicable to symptom control in pediatric oncology is increasing but remains small. Improving the creation of and adherence to CPGs for symptom management is an important priority. Finally, identifying ways that symptom management systems can be integrated into clinical work flows is essential; these will likely need to focus on electronic health records.
- Published
- 2019
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44. Abnormal preschool Lung Clearance Index (LCI) reflects clinical status and predicts lower spirometry later in childhood in cystic fibrosis.
- Author
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Hardaker KM, Panda H, Hulme K, Wong A, Coward E, Cooper P, Fitzgerald DA, Pandit C, Towns S, Selvadurai H, and Robinson PD
- Subjects
- Aftercare methods, Child, Child, Preschool, Early Diagnosis, Equipment Design, Female, Health Status Indicators, Humans, Male, Outcome Assessment, Health Care, Predictive Value of Tests, Prognosis, Breath Tests methods, Cystic Fibrosis diagnosis, Cystic Fibrosis physiopathology, Mucociliary Clearance, Respiratory Function Tests methods, Respiratory Function Tests statistics & numerical data, Spirometry methods, Spirometry statistics & numerical data
- Abstract
Background: Clinical and prognostic value of preschool Multiple Breath Washout (MBW) remains unclear., Methods: Initial MBW results (Exhalyzer® D, EcoMedics AG) in preschool Cystic Fibrosis (CF) subjects (age 2-6 years) at a time of clinical stability were compared to (1) concurrent clinical status measures and (2) later spirometry outcomes. Abnormal Lung Clearance Index (LCI) was defined using published reference data (ULN for LCI 8.0)., Results: LCI was abnormal in 56% (28/50), with mean (SD) LCI 8.61(1.85) at age 4.71(1.3) years. Abnormal LCI was associated with higher dornase alfa use, previous positive bacterial cultures and pF508.del homozygous genotype. Later spirometry (n = 44; mean (SD) 2.3(0.5) years after MBW) demonstrated that abnormal initial preschool LCI was a strong predictor of lower later spirometry outcomes., Conclusion: Abnormal preschool LCI was associated with concurrent measures of clinical status and later spirometry deficits, suggesting early prognostic utility of MBW testing in this age range., (Copyright © 2019. Published by Elsevier B.V.)
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- 2019
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45. Efficacy of antibiotic prophylaxis in patients with cancer and hematopoietic stem cell transplantation recipients: A systematic review of randomized trials.
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Egan G, Robinson PD, Martinez JPD, Alexander S, Ammann RA, Dupuis LL, Fisher BT, Lehrnbecher T, Phillips B, Cabral S, Tomlinson G, and Sung L
- Subjects
- Adult, Anti-Bacterial Agents therapeutic use, Bacteremia prevention & control, Child, Humans, Randomized Controlled Trials as Topic, Treatment Outcome, Antibiotic Prophylaxis methods, Antineoplastic Agents adverse effects, Bacteremia epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Neoplasms therapy
- Abstract
Purpose: To determine the efficacy and safety of different prophylactic systemic antibiotics in adult and pediatric patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation (HSCT)., Methods: We conducted a systematic review and performed searches of Ovid MEDLINE, MEDLINE in-process and Embase; and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were HSCT recipients with anticipated neutropenia, and the intervention was systemic antibacterial prophylaxis. Strategies synthesized included fluoroquinolone vs no antibiotic/nonabsorbable antibiotic; fluoroquinolone vs trimethoprim-sulfamethoxazole; trimethoprim-sulfamethoxazole vs no antibiotic; and cephalosporin vs. no antibiotic. Fluoroquinolone vs cephalosporin and levofloxacin vs ciprofloxacin were compared by network meta-analysis. Primary outcome was bacteremia., Results: Of 20 984 citations screened, 113 studies comparing prophylactic antibiotic to control were included. The following were effective in reducing bacteremia: fluoroquinolone vs no antibiotic/nonabsorbable antibiotic (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.41-0.76), trimethoprim-sulfamethoxazole vs no antibiotic (RR 0.59, 95% CI 0.41-0.85) and cephalosporin vs no antibiotic (RR 0.30, 95% CI 0.16-0.58). Fluoroquinolone was not significantly associated with increased Clostridium difficile infection (RR 0.62, 95% CI 0.31-1.24) or invasive fungal disease (RR 1.28, 95% CI 0.79-2.08) but did increase resistance to fluoroquinolone among bacteremia isolates (RR 3.35, 95% CI 1.12 to 10.03). Heterogeneity in fluoroquinolone effect on bacteremia was not explained by evaluated study, population, or methodological factors. Network meta-analysis revealed no direct comparisons for pre-specified analyses; superior regimens were not identified., Conclusions: Fluoroquinolone, trimethoprim-sulfamethoxazole, and cephalosporin prophylaxis reduced bacteremia. A clinical practice guideline to facilitate prophylactic antibiotic decision-making is required., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2019
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46. Home-based Forced Oscillation Technique Day-to-Day Variability in Pediatric Asthma.
- Author
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Wong A, Hardaker K, Field P, Huvanandana J, King GG, Reddel H, Selvadurai H, Thamrin C, and Robinson PD
- Subjects
- Adolescent, Asthma physiopathology, Child, Home Care Services, Humans, Monitoring, Physiologic methods, Asthma diagnosis, Respiratory Function Tests methods
- Published
- 2019
- Full Text
- View/download PDF
47. Contribution of peripheral airway function to changes in FEV 1 /FVC and RV/TLC with aging.
- Author
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Htun C, Pope A, Lahzami S, Luo D, Schoeffel RE, Farrow CE, Phillips CL, Robinson PD, and King GG
- Subjects
- Adult, Aged, Cross-Sectional Studies, Female, Healthy Volunteers, Humans, Male, Middle Aged, Respiratory Function Tests, Aging physiology, Bronchioles physiology
- Abstract
Multiple breath nitrogen washout (MBNW) indices provide insight into ventilation heterogeneity globally [lung clearance index (LCI)] and within acinar (S
acin ) and conducting (Scond ) airways. Normal aging leads to an accelerated deterioration of Sacin in older adults, but little is known about the contribution of peripheral airway function to changes in pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] with aging. We aimed to examine associations between MBNW and FEV1 /FVC as well as RV/TLC in healthy adults, and to determine if these relationships differ in older (≥50 yr) versus younger subjects (<50 yr). Seventy-nine healthy adult volunteers aged 23-89 yr with no cardiac or respiratory disease and a smoking history of <5 pack-years underwent spirometry, plethysmography, and MBNW. After adjustment for sex, height, and body mass index, the following relationships were present across the entire cohort: Sacin was inversely related to FEV1 /FVC (R2 = 0.22, P < 0.001); Sacin and Scond were positively related to RV/TLC (R2 = 0.53, P < 0.001); on separate analyses, the relationship between Sacin and FEV1 /FVC was strongest in the older group (R2 = 0.20, P = 0.003) but markedly weaker in the younger group (R2 = 0.09, P = 0.04); and Sacin and Scond were related to RV/TLC in older (R2 = 0.20, P = 0.003) but not younger subgroups. No relationships were observed between LCI and FEV1 /FVC or RV/TLC. Changes in FEV1 /FVC and RV/TLC are at least in part due to changes in peripheral airway function with aging. Further studies of the relationships between MBNW and standard pulmonary function indices may prove useful for their combined application and interpretation in obstructive airways disease. NEW & NOTEWORTHY This study explores associations between multiple breath nitrogen washout (MBNW) and standard pulmonary function indices reflecting expiratory airflow [forced expiratory volume in one second (FEV1 )/forced vital capacity (FVC)] and gas trapping [residual volume (RV)/total lung capacity (TLC)] in healthy adults across a wide range of ages. We have demonstrated statistically significant relationships between MBNW and FEV1 /FVC as well as RV/TLC. These findings provide novel evidence of the contribution of peripheral airway function to changes in standard pulmonary function indices with aging.- Published
- 2018
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48. Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.
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Fisher BT, Robinson PD, Lehrnbecher T, Steinbach WJ, Zaoutis TE, Phillips B, and Sung L
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- Adolescent, Adrenal Cortex Hormones adverse effects, Age Factors, Antineoplastic Agents adverse effects, Child, Graft vs Host Disease complications, Humans, Immunosuppressive Agents adverse effects, Invasive Fungal Infections drug therapy, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute drug therapy, Neoplasms drug therapy, Neoplasms immunology, Neutropenia chemically induced, Neutropenia complications, Risk Factors, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections diagnosis, Neoplasms therapy
- Abstract
Background: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed., Methods: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD., Results: Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts., Conclusions: With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.
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- 2018
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49. Comparison of facemask and mouthpiece interfaces for multiple breath washout measurements.
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Robinson PD, Lum S, Moore C, Hardaker KM, Benseler N, Aurora P, Cooper P, Fitzgerald D, Jensen R, McDonald R, Selvadurai H, Ratjen F, and Stanojevic S
- Subjects
- Adult, Anatomy, Regional, Breath Tests instrumentation, Breath Tests methods, Child, Child, Preschool, Feasibility Studies, Female, Functional Residual Capacity physiology, Humans, Male, Mouth anatomy & histology, Nose anatomy & histology, Respiration, Cystic Fibrosis diagnosis, Equipment Design, Face anatomy & histology, Masks, Respiratory Function Tests instrumentation, Respiratory Function Tests methods
- Abstract
Background: Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children., Methods: We investigated the effect of interface choice and breathing modalities on MBW outcomes in healthy adults and preschool children., Results: In adults (n = 26) facemask breathing significantly increased LCI, compared to mouthpiece use (mean difference (95% CI) 0.4 (0.2; 0.6)), with results generalizable across sites and different equipment. Exclusively nasal breathing within the facemask increased LCI, as compared to oral breathing. In preschoolers (2-6 years, n = 46), no significant inter-test difference was observed across interfaces for LCI or FRC. Feasibility and breathing stability were significantly greater with facemask (incorporating dead space volume minimization), vs. mouthpiece. This was more pronounced in subjects <4 years of age., Conclusion: Both nasal vs. oral breathing and mouthpiece vs. facemask affect LCI measurements in adults. This effect was minimal in preschool children, where switching between interfaces is most likely to occur., (Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)
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- 2018
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50. Ventilation inhomogeneity and NO and CO diffusing capacity in ex-premature school children.
- Author
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Sørensen JK, Buchvald F, Berg AK, Robinson PD, and Nielsen KG
- Subjects
- Adolescent, Birth Weight physiology, Bronchodilator Agents therapeutic use, Bronchopulmonary Dysplasia drug therapy, Carbon Monoxide, Case-Control Studies, Child, Female, Follow-Up Studies, Gestational Age, Humans, Infant, Newborn, Male, Nitric Oxide, Premature Birth physiopathology, Pulmonary Diffusing Capacity drug effects, Spirometry methods, Bronchopulmonary Dysplasia physiopathology, Infant, Premature physiology, Pulmonary Diffusing Capacity physiology
- Abstract
Aim: Ex-premature school children show mild-to-moderate airway obstruction and decreased CO diffusing capacity. Multiple breath nitrogen washout (N2MBW) and NO diffusing capacity (DLNO) measurements may provide new insight into long-term pulmonary and vascular impairment in bronchopulmonary dysplasia (BPD)., Methods: We examined a randomly selected group of 70 ex-premature children (gestational age <28 weeks or birth weight <1500 g; 42 with and 28 without BPD) and 38 term-born healthy controls of 8-13 years of age. Subjects performed N2MBW (lung clearance index, LCI; Sacin, and Scond), DLNO (membrane related diffusing capacity, Dm and pulmonary capillary volume, Vc), Fractional exhaled NO, CO diffusing capacity, conventional spirometry (FEV1, FVC, FEF25-75) and plethysmography (RV, TLC). Respiratory symptoms were assessed by questionnaire., Results: Compared to healthy controls, the BPD group had higher z-scores for lung clearance index (P = 0.003), Sacin (P = 0.005), lower CO diffusing capacity (P = 0.025), DLNO (P = 0.022), DLNO/VA z-scores (P = 0.025) and a significant larger proportion had respiratory complaints. Amongst ex-premature children, the BPD group did not differ from the non-BPD group except for a decreased Dm (P = 0.023). Ex-premature with BPD showed predominantly airway obstruction (FEV1/FVC; P < 0.0001), signs of hyperinflation (RV/TLC-ratio; P = 0.028), and 25% had a positive bronchodilator response (>12% in FEV1)., Conclusion: Ex-premature school children exhibited relatively mild but significant long-term respiratory symptoms and pulmonary peripheral impairment judged by N2MBW and DLNO measurements along with well-known airway obstruction. Larger longitudinal studies are needed to assess the clinical use of these advanced methods of assessing ventilation inhomogeneity and DLNO., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
- Full Text
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