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1. Phenotyping OSAH patients during wakefulness

Author: Pini, L., Magri, R., Perger, E., Levi, G., Zambelli, L., Giordani, J., Ciarfaglia, M., and Tantucci, C.
Published: 2022
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2. Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention

Author: Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., Protti G., Baldassarre, D, Iacoviello, L, Baetta, R, Roncaglioni, M, Condorelli, G, Remuzzi, G, Gensini, G, Frati, L, Ricciardi, W, Conaldi, P, Uccelli, A, Blandini, F, Bosari, S, Scambia, G, Fini, M, Di Malta, A, Amato, M, Veglia, F, Bonomi, A, Klersy, C, Colazzo, F, Pengo, M, Gorini, F, Auteri, L, Ferrante, G, Baviera, M, Ambrosio, G, Catapano, A, Gialluisi, A, Malavazos, A, Castelvecchio, S, Corsi-Romanelli, M, Cardani, R, La Rovere, M, Agnese, V, Pane, B, Prati, D, Spinardi, L, Liuzzo, G, Arbustini, E, Volterrani, M, Visconti, M, Werba, J, Genovese, S, Bilo, G, Invitti, C, Di Blasio, A, Lombardi, C, Faini, A, Rosa, D, Ojeda-Fernandez, L, Foresta, A, De Curtis, A, Di Castelnuovo, A, Scalvini, S, Pierobon, A, Gorini, A, Valenti, L, Luzi, L, Racca, A, Bandi, M, Tremoli, E, Menicanti, L, Parati, G, Pompilio, G, Colombo, G, Vavassori, C, Biondi, M, Frigerio, B, Ravani, A, Sansaro, D, Coggi, D, Romandini, A, Giroli, M, Giuliani, M, Bonmi, A, Rondinelli, M, Trudu, C, Cinieri, C, Monturano, M, Colazo, F, Inviti, C, Di Blasi, A, Torlasco, C, Gilardini, L, Soranna, D, Zambon, A, Perger, E, Zanotti, L, Badano, L, Cova, L, Gentilini, D, Grappiolo, L, Condoreli, G, Ferante, G, Papa, L, Savevski, V, Ieva, F, Romano, I, Remzzi, G, Ojeda, L, Clerici, F, Palumbo, A, Genini, G, Catpano, A, Mattioli, R, Longhi, E, Mantovani, L, Madotto, F, Bonaccio, M, Gianfagna, F, Ghulam, A, Magnacca, S, Noro, F, Costanzo, S, Esposito, S, Orlandi, S, Persichillo, M, Bracone, F, Panzera, T, Ruggiero, E, Parisi, R, Franciosa, S, Morelli, M, De Rita, F, Cerletti, C, de Gaetano, G, Donati, M, Mencanti, L, Romanelli, M, Cerri, A, Dubini, C, Trevisan, M, Renna, L, Milani, V, Boveri, S, Giubbilini, P, Ramputi, L, Baroni, I, De Angeli, G, Riciardi, W, Olmetti, F, Bussotti, M, Gaetano, C, Baiardi, P, Bachetti, T, Balbi, M, Comini, L, Lorenzoni, M, Olivares, A, Traversi, E, Garre, C, Sideri, R, Clemenza, F, Gentile, G, Caruana, G, Cuscino, N, Di Gesaro, G, Greco, A, Loddo, I, Tuzzolino, F, Ucelli, A, Palombo, D, Spinella, G, Mozzetta, G, Ameri, P, Zoppoli, G, Finotello, A, Porto, I, Pratesi, G, Bladini, F, Spnardi, L, Clerici, M, Pelusi, S, Bianco, C, Carpani, R, Periti, G, Margarita, S, Lanza, G, Severino, A, Pedicino, D, D'Amario, D, D'Aiello, A, Vinci, R, Bonanni, A, Brecciaroli, M, Filomia, S, Pastorino, R, Boccia, S, Urbani, A, Sanguinetti, M, Santoliquido, A, Proto, L, Tarquini, D, Grimaldi, M, Leonardi, S, Elia, A, Currao, A, Urtis, M, Di Toro, A, Giuliani, L, Caminiti, G, Marcolongo, F, Sposato, B, Guadagni, F, Morsella, V, Marziale, A, Protti, G, Baldassarre D., Iacoviello L., Baetta R., Roncaglioni M. C., Condorelli G., Remuzzi G., Gensini G., Frati L., Ricciardi W., Conaldi P. G., Uccelli A., Blandini F., Bosari S., Scambia G., Fini M., Di Malta A., Amato M., Veglia F., Bonomi A., Klersy C., Colazzo F., Pengo M., Gorini F., Auteri L., Ferrante G., Baviera M., Ambrosio G., Catapano A., Gialluisi A., Malavazos A. E., Castelvecchio S., Corsi-Romanelli M. M., Cardani R., La Rovere M. T., Agnese V., Pane B., Prati D., Spinardi L., Liuzzo G., Arbustini E., Volterrani M., Visconti M., Werba J. P., Genovese S., Bilo G., Invitti C., Di Blasio A., Lombardi C., Faini A., Rosa D., Ojeda-Fernandez L., Foresta A., De Curtis A., Di Castelnuovo A., Scalvini S., Pierobon A., Gorini A., Valenti L., Luzi L., Racca A., Bandi M., Tremoli E., Menicanti L., Parati G., Pompilio G., Colombo G., Vavassori C., Biondi M. L., Frigerio B., Ravani A., Sansaro D., Coggi D., Romandini A., Giroli M., Giuliani M., Bonmi A., Rondinelli M., Trudu C., Cinieri C., Monturano M., Colazo F., Inviti C., Di Blasi A., Torlasco C., Gilardini L., Soranna D., Zambon A., Perger E., Zanotti L., Badano L., Cova L., Gentilini D., Grappiolo L., Condoreli G., Ferante G., Papa L., Savevski V., Ieva F., Romano I., Remzzi G., Ojeda L., Clerici F., Palumbo A., Genini G. F., Catpano A., Mattioli R., Longhi E., Mantovani L. G., Madotto F., Bonaccio M., Gianfagna F., Ghulam A., Magnacca S., Noro F., Costanzo S., Esposito S., Orlandi S., Persichillo M., Bracone F., Panzera T., Ruggiero E., Parisi R., Franciosa S., Morelli M., De Rita F., Cerletti C., de Gaetano G., Donati M. B., Mencanti L., Romanelli M. M. C., Cerri A., Dubini C., Trevisan M. B., Renna L. V., Milani V., Boveri S., Giubbilini P., Ramputi L., Baroni I., De Angeli G., Riciardi W., Olmetti F., Bussotti M., Gaetano C., Baiardi P., Bachetti T., Balbi M., Comini L., Lorenzoni M., Olivares A., Traversi E., Garre C., Sideri R., Clemenza F., Gentile G., Caruana G., Cuscino N., Di Gesaro G., Greco A., Loddo I., Tuzzolino F., Ucelli A., Palombo D., Spinella G., Mozzetta G., Ameri P., Zoppoli G., Finotello A., Porto I., Pratesi G., Bladini F., Spnardi L., Clerici M., Pelusi S., Bianco C., Carpani R., Periti G., Margarita S., Lanza G. A., Severino A., Pedicino D., D'Amario D., D'Aiello A., Vinci R., Bonanni A., Brecciaroli M., Filomia S., Pastorino R., Boccia S., Urbani A., Sanguinetti M., Santoliquido A., Proto L., Tarquini D., Grimaldi M. C., Leonardi S., Elia A., Currao A., Urtis M., Di Toro A., Giuliani L., Caminiti G., Marcolongo F., Sposato B., Guadagni F., Morsella V., Marziale A., and Protti G.
Abstract: Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's
Published: 2023

3. Clinical Value of a Novel Three-Dimensional Echocardiography–Derived Index of Right Ventricle–Pulmonary Artery Coupling in Tricuspid Regurgitation

Author: Gavazzoni, M, Badano, L, Cascella, A, Heilbron, F, Tomaselli, M, Caravita, S, Baratto, C, Perelli, F, Radu, N, Perger, E, Parati, G, Muraru, D, Gavazzoni M., Badano L., Cascella A., Heilbron F., Tomaselli M., Caravita S., Baratto C., Perelli F., Radu N., Perger E., Parati G., Muraru D., Gavazzoni, M, Badano, L, Cascella, A, Heilbron, F, Tomaselli, M, Caravita, S, Baratto, C, Perelli, F, Radu, N, Perger, E, Parati, G, Muraru, D, Gavazzoni M., Badano L., Cascella A., Heilbron F., Tomaselli M., Caravita S., Baratto C., Perelli F., Radu N., Perger E., Parati G., and Muraru D.
Abstract: Background: Echocardiographic surrogates of right ventricle–to–pulmonary artery (RV-PA) coupling have been reported to be associated with outcomes in patients with secondary tricuspid regurgitation (STR). However, pulmonary artery systolic pressure (PASP) is difficult to estimate using echocardiography in patients with severe STR. The aim of the present study was to evaluate the predictive power of a surrogate of RV-PA coupling obtained using right ventricular (RV) volumes measured on three-dimensional echocardiography. Methods: One hundred eight patients (mean age, 73 ± 13 years; 61% women) with moderate or severe STR were included. Results: At a median follow-up of 24 months (interquartile range, 2-48 months), 72 patients (40%) had reached the composite end point of death of any cause and heart failure hospitalization. RV-PA coupling was computed as the ratio between RV forward stroke volume (SV) (i.e., RV SV − regurgitant volume) and RV end-systolic volume (ESV). RV forward SV/ESV was significantly more related to the composite end point than RV ejection fraction (area under the curve, 0.85 [95% CI, 0.78-0.93] vs 0.73 [95% CI, 0.64-0.83], respectively; P = .03). A value of 0.40 was found to best correlate with outcome. On multivariate Cox regression, RV forward SV/ESV, tricuspid annular plane systolic excursion/PASP, and RV free wall longitudinal strain/PASP were all independently associated with the occurrence of the composite end point when added to a group of parameters including STR severity (severe vs moderate), atrial fibrillation, pulmonary arterial hypertension, right atrial volume, RV end-diastolic volume, and RV free wall longitudinal strain. RV forward SV/ESV < 0.40 (HR, 3.36; 95% CI, 1.49-7.56; P < .01) carried higher related risk than RV free wall longitudinal strain/PASP < −0.42%/mm Hg (HR, 3.1; 95% CI, 1.26-7.84; P = .01) and tricuspid annular plane systolic excursion/PASP < 0.36 mm/mm Hg (HR, 2.69; 95% CI, 1.29-5.58; P = .01). RV eject
Published: 2023

4. Sleep-Disordered Breathing and Chronic Respiratory Infections: A Narrative Review in Adult and Pediatric Population

Author: Faverio, P, Zanini, U, Monzani, A, Parati, G, Luppi, F, Lombardi, C, Perger, E, Faverio P., Zanini U., Monzani A., Parati G., Luppi F., Lombardi C., Perger E., Faverio, P, Zanini, U, Monzani, A, Parati, G, Luppi, F, Lombardi, C, Perger, E, Faverio P., Zanini U., Monzani A., Parati G., Luppi F., Lombardi C., and Perger E.
Abstract: Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.
Published: 2023

5. Effects of short-term exposure to particulate matter on emergency department admission and hospitalization for asthma exacerbations in Brescia district

Author: Pini, L, Giordani, J, Concoreggi, C, Zanardini, E, Pini, A, Perger, E, Bargagli, E, Di Bona, D, Ciarfaglia, M, Tantucci, C, Pini L., Giordani J., Concoreggi C., Zanardini E., Pini A., Perger E., Bargagli E., Di Bona D., Ciarfaglia M., Tantucci C., Pini, L, Giordani, J, Concoreggi, C, Zanardini, E, Pini, A, Perger, E, Bargagli, E, Di Bona, D, Ciarfaglia, M, Tantucci, C, Pini L., Giordani J., Concoreggi C., Zanardini E., Pini A., Perger E., Bargagli E., Di Bona D., Ciarfaglia M., and Tantucci C.
Abstract: Background: Rising pollution plays a crucial role in worsening several respiratory diseases. Particulate Matter (PM)-induced asthma exacerbations are one of the most dangerous events. Objectives: To assess the correlation between progressive particulate matter short-term exposure and asthma exacerbations, we investigated the role of PM levels on Emergency Department (ED) admissions and hospitalizations for these events in Brescia, an important industrial city located in northern Italy with high yearly levels of air pollution. Methods: We analyzed 1050 clinical records of ED admissions for suspected asthma exacerbation, starting from January 2014 to December 2017. Daily PM levels were collected from the Environmental Protection Regional Agency. We performed a time-series analysis using a Poisson regression model with single and multiple day-lag. Results were expressed as Relative Risk (RR) and Excess of Relative Risk (ERR) of severe asthma exacerbation over a 10 µg/m3 increase in PM10 and PM2.5 concentration. Results: We selected and focused our analysis on 543 admissions for indisputable asthma exacerbation in ED and hospital. The time-series study showed an increase of the RR (CI95%) for asthma exacerbation-related ED admissions of 1.24 with an ERR of 24.2% for PM2.5 at lag0–1 (p < 0.05). We also estimated for PM2.5 a RR (CI95%) of 1.12 with an ERR of 12.5% at lag0–5 (p ≤ 0.05). Again, for PM2.5, an increase of the RR (CI95%) for asthma exacerbation-related hospitalizations of 1.31 with an ERR of 30.7% at lag0–1 (p < 0.05) has been documented. These findings were confirmed and even reinforced considering only the population living in the city. Conclusions: Short-term PM exposure, especially for PM2.5, plays a critical role in inducing asthma exacerbation events leading to ED admission or hospitalization.
Published: 2022

6. Phenotyping OSAH patients during wakefulness

Author: Pini, L, Magri, R, Perger, E, Levi, G, Zambelli, L, Giordani, J, Ciarfaglia, M, Tantucci, C, Pini L., Magri R., Perger E., Levi G., Zambelli L., Giordani J., Ciarfaglia M., Tantucci C., Pini, L, Magri, R, Perger, E, Levi, G, Zambelli, L, Giordani, J, Ciarfaglia, M, Tantucci, C, Pini L., Magri R., Perger E., Levi G., Zambelli L., Giordani J., Ciarfaglia M., and Tantucci C.
Abstract: Purpose: Although currently there are simplified methods to measure the pathophysiological traits that stimulate the occurrence and maintenance of obstructive sleep apnea–hypopnea (OSAH), they remain difficult to implement in routine practice. This pilot study aimed to find a simpler daytime approach to obtain a meaningful, similar pathophysiological phenotypic profile in patients with OSAH. Methods: After obtaining diagnostic polygraphy from a group of consecutive patients with OSAH, we performed the dial-down CPAP technique during nocturnal polysomnography and used it as reference method. This allowed assessment of upper airway collapsibility, loop gain (LG), arousal threshold (AT), and upper airway muscle gain (UAG). We compared these results with a daytime protocol based on negative expiratory pressure (NEP) technique for evaluating upper airway collapsibility and UAG, on maximal voluntary apnea for LG, and on clinical predictors for AT. Results: Of 15 patients studied, 13 patients with OSAH accurately completed the two procedures. There were strong (all r2 > 0.75) and significant (all p < 0.001) correlations for each phenotypic trait between the measurements obtained through the reference method and those achieved during wakefulness. Conclusion: It is possible to phenotype patients with OSAH from a pathophysiological point of view while they are awake. Using this approach, cutoff values corresponding to those usually adopted using the reference method can be identified to detect abnormal traits, achieving profiles similar to those obtained through the dial-down CPAP technique.
Published: 2022

7. Obstructive Sleep Apnea and Adherence to Continuous Positive Airway Pressure (CPAP) Treatment: Let’s Talk about Partners!

Author: Rosa, D, Amigoni, C, Rimoldi, E, Ripa, P, Ligorio, A, Fracchiolla, M, Lombardi, C, Parati, G, Perger, E, Rosa D., Amigoni C., Rimoldi E., Ripa P., Ligorio A., Fracchiolla M., Lombardi C., Parati G., Perger E., Rosa, D, Amigoni, C, Rimoldi, E, Ripa, P, Ligorio, A, Fracchiolla, M, Lombardi, C, Parati, G, Perger, E, Rosa D., Amigoni C., Rimoldi E., Ripa P., Ligorio A., Fracchiolla M., Lombardi C., Parati G., and Perger E.
Abstract: Background: Continuous positive airway pressure (CPAP) is the gold standard treatment for obstructive sleep apnea (OSA). The benefits of this therapy were studied and analyzed over time; patient adherence is often poor, as many factors negatively influence it. A topic that needs clarification is whether adherence to CPAP treatment in a patient with OSA is influenced by the behavior of a partner or spouse. Methods: A scoping review was conducted to evaluate the role of partner involvement in the CPAP treatment management in a patient with OSA. The research project was performed between August and September 2021 by consulting the main biomedical databases: CINHAL, Embase, PsycINFO, and PubMed. Results: Among 21 articles considered valid for our aim, 15 are qualitative studies, 5 are quantitative and 1 presents a mixed method. We identified several thematic areas and “key” elements, which are prevalent in the studies evaluated. Conclusions: The presence of a partner promotes adherence to CPAP therapy in patients with OSA, resulting in ameliorating their overall quality of life. To increase CPAP adherence, a trained nurse could represent a reference figure to technically and emotionally support couples during the adaptation period and in the long term.
Published: 2022

8. Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world

Author: Perger, E, Baillieul, S, Esteve, F, Pichon, A, Bilo, G, Soranna, D, Doutreleau, S, Savina, Y, Ulliel-Roche, M, Brugniaux, J, Stauffer, E, Oberholzer, L, Howe, C, Hannco, I, Lombardi, C, Tamisier, R, Pepin, J, Verges, S, Parati, G, Perger E., Baillieul S., Esteve F., Pichon A., Bilo G., Soranna D., Doutreleau S., Savina Y., Ulliel-Roche M., Brugniaux J. V., Stauffer E., Oberholzer L., Howe C., Hannco I., Lombardi C., Tamisier R., Pepin J. -L., Verges S., Parati G., Perger, E, Baillieul, S, Esteve, F, Pichon, A, Bilo, G, Soranna, D, Doutreleau, S, Savina, Y, Ulliel-Roche, M, Brugniaux, J, Stauffer, E, Oberholzer, L, Howe, C, Hannco, I, Lombardi, C, Tamisier, R, Pepin, J, Verges, S, Parati, G, Perger E., Baillieul S., Esteve F., Pichon A., Bilo G., Soranna D., Doutreleau S., Savina Y., Ulliel-Roche M., Brugniaux J. V., Stauffer E., Oberholzer L., Howe C., Hannco I., Lombardi C., Tamisier R., Pepin J. -L., Verges S., and Parati G.
Abstract: Introduction: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. Methods: Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude. Results: Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= −0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders. Conclusions: Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progre
Published: 2022

9. Lung Ultrasound in Patients With SARS-COV-2 Pneumonia: Correlations With Chest Computed Tomography, Respiratory Impairment, and Inflammatory Cascade

Author: Fratianni, G, Malfatto, G, Perger, E, Facchetti, L, Pini, L, Bosco, M, Cernigliaro, F, Perego, G, Facchini, M, Badano, L, Parati, G, Fratianni G., Malfatto G., Perger E., Facchetti L., Pini L., Bosco M., Cernigliaro F., Perego G. B., Facchini M., Badano L., Parati G., Fratianni, G, Malfatto, G, Perger, E, Facchetti, L, Pini, L, Bosco, M, Cernigliaro, F, Perego, G, Facchini, M, Badano, L, Parati, G, Fratianni G., Malfatto G., Perger E., Facchetti L., Pini L., Bosco M., Cernigliaro F., Perego G. B., Facchini M., Badano L., and Parati G.
Abstract: Objectives: Lung ultrasound (LUS) might be comparable to chest computed tomography (CT) in detecting parenchymal and pleural pathology, and in monitoring interstitial lung disease. We aimed to describe LUS characteristics of patients during the hospitalization for COVID-19 pneumonia, and to compare the extent of lung involvement at LUS and chest-CT with inflammatory response and the severity of respiration impairment. Methods: During a 2-week period, we performed LUS and chest CT in hospitalized patients affected by COVID-19 pneumonia. Dosages of high sensitivity C-reactive protein (HS-CRP), d-dimer, and interleukin-6 (IL-6) were also obtained. The index of lung function (P/F ratio) was calculated from the blood gas test. LUS and CT scoring were assessed using previously validated scores. Results: Twenty-six consecutive patients (3 women) underwent LUS 34 ± 14 days from the early symptoms. Among them, 21 underwent CT on the same day of LUS. A fair association was found between LUS and CT scores (R = 0.45, P =.049), which became stronger if the B-lines score on LUS was not considered (R = 0.57, P =.024). LUS B-lines score correlated with IL-6 levels (R = 0.75, P =.011), and the number of involved lung segments detected by LUS correlated with the P/F ratio (R = 0.60, P =.019) but not with HS-CRP and d-Dimer levels. No correlations were found between CT scores and inflammations markers or P/F. Conclusion: In patients with COVID-19 pneumonia, LUS was correlated with both the extent of the inflammatory response and the P/F ratio.
Published: 2022

10. SLEEP APNEA AND HYPOXIA: NEW THERAPEUTIC PROSPECTIVES

Author: Perger, E, PARATI, GIANFRANCO, LOMBARDI, CAROLINA, PERGER, ELISA, Perger, E, PARATI, GIANFRANCO, LOMBARDI, CAROLINA, and PERGER, ELISA
Abstract: Un terzo della popolazione europea è affetta da apnee ostruttive del sonno (OSA), patologia che ha conseguenze negative su morbilità cardiovascolare e qualità della vita. L’OSA è caratterizzata da ripetuti episodi di collasso delle alte vie respiratorie che determinano ipossia intermittente, modifiche della pressione intratoracica e risvegli corticali. L’ipossia intermittente ha un ruolo chiave nel determinare le conseguenze cardiovascolari dei disturbi del respiro nel sonno e può sovrapporsi, peggiorandone la prognosi, a condizioni caratterizzate da ipossia tonica quali l’alta quota o le patologie respiratorie croniche o infettive, esacerbando lo stress ossidativo, l’angiogenesi e quindi l’attivazione del sistema nervoso simpatico con conseguenti incrementi della pressione arteriosa, della frequenza cardiaca e dell’infiammazione. Il trattamento gold standard per l’OSA è la terapia ventilatoria che risulta però non tollerata dalla metà dei pazienti che ne fanno uso. Nuove strategie terapeutiche sono pertanto auspicabili. Recentemente sono stati identificati specifici fattori fisiopatologici che contribuiscono allo sviluppo dell’OSA: un’elevata collassabilità delle vie aeree superiori, l’instabilità del sistema di controllo del respiro, una ridotta soglia di arousal ed una ridotta risposta compensatoria dei muscoli dilatatori della faringe. Quest’ultima è dovuta alla perdita di attività noradrenergica e aumento delle influenze muscariniche alle alte vie aeree. Il riconoscimento di questi tratti fisiopatologici ha permesso di ipotizzare e sviluppare nuove strategie terapeutiche per l’OSA. Obiettivo: Valutare l’efficacia della somministrazione per 1 settimana della combinazione di reboxetina (noradrenergico) ed ossibutinina (antimuscarinico) sul trattamento dell’OSA e dell’effetto dei farmaci sugli endotipi fisiopatologici. Metodi: E’ stato condotto uno studio randomizzato controllato cross-over in doppio cieco per comparare 4mg di reboxetina più 5mg di os, Introduction: Obstructive sleep apnea (OSA) affects one third of the population in Europe and has major negative consequences for cardiovascular disease and quality of life. OSA is characterized by recurrent episodes of apneas and hypopneas associated with repetitive episodes of intermittent hypoxemia, intrathoracic pressure changes, and arousals. Intermittent hypoxemia, particularly with concomitant hypercapnia, activates the sympathetic nervous system and it is the major contributor to negative cardiovascular consequences. Intermittent hypoxia might also worsen concomitant tonic hypoxia due to high altitude or due to acute or chronic respiratory diseases by promoting oxidative stress and angiogenesis, thus increasing sympathetic activation with blood pressure elevation, inflammation and endothelial dysfunction. Although OSA and its hypoxic consequence are effectively alleviated with positive airways pressure, this treatment is yet unsatisfactory, being poorly tolerated by up to half of patients. Thus, new treatment strategies are strongly needed. With the aim of better understand OSA physiopathology, key contributors of its development have been identified and include upper airway collapsibility, ventilatory instability, low arousal threshold and reduced pharyngeal dilator muscle responsiveness during sleep, due to loss of noradrenergic drive and enhanced muscarinic influences to upper airway muscles. The recognition of these pathophysiological traits permitted to advance the research in the field of OSA new therapeutic perspectives. Aim: The aim of this study was to evaluate the effect of 1-week of reboxetine (a noradrenergic) plus oxybutynin (an antimuscarinic) on OSA severity (primary outcome) and their effect on endotypic traits and cardiovascular autonomic modulation. Methods: We performed a randomized, placebo-controlled, double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin (reb–oxy) to placebo in OSA subjects. After a baseline in-lab
Published: 2023

11. Italian good practice recommendations on management of persons with Long-COVID

Author: Giuliano, M., Tiple, D., Agostoni, P., Armocida, B., Biardi, L., Bonfigli, A.R., Campana, A., Ciardi, M., Di Marco, F., Floridia, M., Gnerre, P., Grassi, T., Grattagliano, I., Kruger, P., Leonardi, M., Liguori, R., Pagani, E., Perger, E., Pricci, F., Ruggeri, M., Silenzi, A., Spannella, F., Tascini, C., Teté, G., Tosato, M., Vecchi, S., Villa, M., and Onder, G.
Subjects: COVID-19, Long COVID, good clinical practices (GCP), Italy, health care systems, guideline, Public Health, Environmental and Occupational Health, Settore MED/11 - Malattie dell'Apparato Cardiovascolare
Abstract: A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient’s needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients.
Published: 2023

12. Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure

Author: Caravita, S., Faini, A., Vignati, C., Pelucchi, S., Salvioni, E., Cattadori, G., Baratto, C., Torlasco, C., Contini, M., Villani, A., Malfatto, G., Perger, E., Lombardi, C., Piperno, A., Agostoni, P., Parati, G., Caravita, S, Faini, A, Vignati, C, Pelucchi, S, Salvioni, E, Cattadori, G, Baratto, C, Torlasco, C, Contini, M, Villani, A, Malfatto, G, Perger, E, Lombardi, C, Piperno, A, Agostoni, P, and Parati, G
Subjects: Male, Anemia, Iron-Deficiency, Iron, Chemoreflex, Stroke Volume, Anaemia, Heart failure, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Iron Deficiencies, Exercise, Sleep, Ferric Compounds, Ventricular Function, Left, Oxygen, Hemoglobins, Sleep Apnea Syndromes, Chronic Disease, Humans, Female, Maltose, Cardiology and Cardiovascular Medicine
Abstract: Aims: Intravenous iron therapy can improve symptoms in patients with heart failure, anaemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns. Methods and results: Patients with heart failure, reduced left ventricular ejection fraction, anaemia (haemoglobin
Published: 2022
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13. BLOOD PRESSURE EFFECTS OF OBSTRUCTIVE SLEEP APNEA TREATMENT BY CONTINUOUS POSITIVE AIRWAY PRESSURE: SYSTEMATIC REVIEW, METAANALYSIS AND EVALUATION OF PHENOTYPES PREDICTING RESPONSE

Author: Pengo, M., Soranna, D., Giontella, A., Perger, E., Schwarz, E.I., Lombardi, C., Bilo, G., Zambon, A., Steier, J., Minuz, P., Parati, G., and Fava, C.
Published: 2019
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14. Improving CPAP Adherence in Adults With Obstructive Sleep Apnea Syndrome: A Scoping Review of Motivational Interventions

Author: Rapelli, G, Pietrabissa, G, Manzoni, G, Bastoni, I, Scarpina, F, Tovaglieri, I, Perger, E, Garbarino, S, Fanari, P, Lombardi, C, Castelnuovo, G, Rapelli G., Pietrabissa G., Manzoni G. M., Bastoni I., Scarpina F., Tovaglieri I., Perger E., Garbarino S., Fanari P., Lombardi C., Castelnuovo G., Rapelli, G, Pietrabissa, G, Manzoni, G, Bastoni, I, Scarpina, F, Tovaglieri, I, Perger, E, Garbarino, S, Fanari, P, Lombardi, C, Castelnuovo, G, Rapelli G., Pietrabissa G., Manzoni G. M., Bastoni I., Scarpina F., Tovaglieri I., Perger E., Garbarino S., Fanari P., Lombardi C., and Castelnuovo G.
Abstract: Objective: This scoping review aims to provide an accessible summary of available evidence on the efficacy of motivational interventions to increase adherence to Continuous Positive Airway Pressure (CPAP) among patients with Obstructive Sleep Apnea Syndrome (OSAS) and of their specific aspects and strategies by assessing adherence measures. Methods: A literature search was performed in PubMed, Scopus, Medline, PsycINFO, and Web of Science databases using the concepts of “obstructive sleep apnea syndrome,” “continuous positive airway pressure,” “motivational intervention,” and “adherence.” Rigorous inclusion criteria and screening by at least two reviewers were applied. Data were extracted to address the review aims and were presented as a narrative synthesis. Results: Search for databases produced 11 randomized controlled trials, all including naïve CPAP users. Findings showed that motivational interventions were more effective than usual care and educational programs in increasing adherence to CPAP, despite results were not always maintained over time across studies. Discussion: To our knowledge, this is the first scoping review of the literature aimed to explore the characteristics and impact of motivational interventions to promote adherence to CPAP in patients with OSAS. More research providing a detailed description of motivational strategies, and testing of their association with positive treatment outcomes via both direct and indirect measures are needed to increase awareness on active mechanisms of change.
Published: 2021

15. Breath-holding as a novel approach to risk stratification in COVID-19

Author: Messineo, L, Perger, E, Corda, L, Joosten, S, Fanfulla, F, Pedroni, L, Terrill, P, Lombardi, C, Wellman, A, Hamilton, G, Malhotra, A, Vailati, G, Parati, G, Sands, S, Messineo L., Perger E., Corda L., Joosten S. A., Fanfulla F., Pedroni L., Terrill P. I., Lombardi C., Wellman A., Hamilton G. S., Malhotra A., Vailati G., Parati G., Sands S. A., Messineo, L, Perger, E, Corda, L, Joosten, S, Fanfulla, F, Pedroni, L, Terrill, P, Lombardi, C, Wellman, A, Hamilton, G, Malhotra, A, Vailati, G, Parati, G, Sands, S, Messineo L., Perger E., Corda L., Joosten S. A., Fanfulla F., Pedroni L., Terrill P. I., Lombardi C., Wellman A., Hamilton G. S., Malhotra A., Vailati G., Parati G., and Sands S. A.
Abstract: Background: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea (‘silent hypoxemia’) in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). Methods: Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. Results: The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. Conclusions: Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.
Published: 2021

16. Diagnostic approach to sleep disordered-breathing among patients with grade III obesity

Author: Perger, E, Aron-Wisnewsky, J, Arnulf, I, Oppert, J, Redolfi, S, Perger E., Aron-Wisnewsky J., Arnulf I., Oppert J. -M., Redolfi S., Perger, E, Aron-Wisnewsky, J, Arnulf, I, Oppert, J, Redolfi, S, Perger E., Aron-Wisnewsky J., Arnulf I., Oppert J. -M., and Redolfi S.
Abstract: Sleep apnea test (SAT) is a cost-effective approach to evaluate subjects without associated comorbidities suspected for obstructive sleep apnea (OSA), a disorder particularly common in obese subjects. The association of obesity with awake hypercapnia (carbon dioxide arterial pressure, PaCO2 ≥45 mmHg) defines the obesity-hypoventilation syndrome (OHS), which in turn results in increased morbidity and mortality compared to simple OSA. Isolated hypoventilation during sleep in obese patients (obesity-related sleep hypoventilation, ORSH) is now considered as an early stage of OHS. The aim of this study was to assess the performance of SAT in diagnosing OSA and predicting the presence of ORHS among patients with grade III obesity without awake hypercapnia. Methods: Over a 14-months period, patients with grade III obesity (body mass index≥40 kg/m2) presenting moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) upon SAT and normal awake PaCO2 at arterial blood gas analysis, systematically underwent in-lab nocturnal polysomnography combined with transcutaneous carbon dioxide pressure (PtcCO2) monitoring. Results: Among 48 patients included in the study, 16 (33%) presented an AHI<15 upon polysomnography and 14 (29%) had ORSH. The test revealed no difference in ORSH prevalence between patients with AHI <15 or ≥15 (31% vs. 25%). No SAT variables were independently associated with increased PtCO2. Conclusions: This study shows that SAT overestimates OSA severity and ORSH affects one third of patients with grade III obesity without awake hypercapnia and with moderate-to-severe OSA at SAT, suggesting how polysomnography combined with PtCO2 monitoring is the most appropriate diagnostic approach for OSA and ORSH in this population.
Published: 2021

17. Subjects with venous insufficiency have high risk of obstructive sleep apnea in relationship to fluid shift

Author: Perger, E, Blaise, S, Vermorel, C, Boge, G, Pepin, J, Redolfi, S, Bosson, J, Perger E., Blaise S., Vermorel C., Boge G., Pepin J. L., Redolfi S., Bosson J. L., Perger, E, Blaise, S, Vermorel, C, Boge, G, Pepin, J, Redolfi, S, Bosson, J, Perger E., Blaise S., Vermorel C., Boge G., Pepin J. L., Redolfi S., and Bosson J. L.
Abstract: Background: Obstructive sleep apnea (OSA) is highly prevalent in conditions characterized by fluid overload. Chronic venous insufficiency (CVI) is associated to fluid overload that might interfere with OSA occurrence and severity. Methods: A total of 180 patients with symptomatic CVI completed the Berlin questionnaire and were assessed for the presence of symptoms and signs of OSA and fluid shift. Results: According to the Berlin questionnaire, 59 patients (33%) had high risk of OSA. The predictors of having a positive Berlin questionnaire were male sex, body mass index and symptoms possibly related to fluid shift. Conclusions: Patients with CVI, a disease characterized by fluid overload, present high risk of OSA, which might be related to fluid shift.
Published: 2020

18. Effect of ultrafiltration on sleep apnea and cardiac function in end-stage renal disease

Author: Inami, T, Lyons, O, Perger, E, Yadollahi, A, Floras, J, Chan, C, Bradley, T, Inami T., Lyons O. D., Perger E., Yadollahi A., Floras J. S., Chan C. T., Bradley T. D., Inami, T, Lyons, O, Perger, E, Yadollahi, A, Floras, J, Chan, C, Bradley, T, Inami T., Lyons O. D., Perger E., Yadollahi A., Floras J. S., Chan C. T., and Bradley T. D.
Abstract: Rationale: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration. Methods: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. -Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no-sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished. Conclusions: In ESRD, cardiac function deteriorates overnight in those with sleep apnea
Published: 2020

19. Obstructive sleep apnoea treatment and blood pressure: Which phenotypes predict a response? A systematic review and meta-analysis

Author: Pengo, M, Soranna, D, Giontella, A, Perger, E, Mattaliano, P, Schwarz, E, Lombardi, C, Bilo, G, Zambon, A, Steier, J, Parati, G, Minuz, P, Fava, C, Pengo M. F., Soranna D., Giontella A., Perger E., Mattaliano P., Schwarz E. I., Lombardi C., Bilo G., Zambon A., Steier J., Parati G., Minuz P., Fava C., Pengo, M, Soranna, D, Giontella, A, Perger, E, Mattaliano, P, Schwarz, E, Lombardi, C, Bilo, G, Zambon, A, Steier, J, Parati, G, Minuz, P, Fava, C, Pengo M. F., Soranna D., Giontella A., Perger E., Mattaliano P., Schwarz E. I., Lombardi C., Bilo G., Zambon A., Steier J., Parati G., Minuz P., and Fava C.
Abstract: The treatment for obstructive sleep apnoea (OSA) with continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is associated with blood pressure (BP) reduction; however, the overall effect is modest. The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effect of such treatments on BP was to identify subgroups of patients who respond best to treatment. The article search was performed in three different databases with specific search terms and selection criteria. From 2289 articles, we included 68 RCTs that compared CPAP or MADs with either passive or active treatment. When all the studies were pooled together, CPAP and MADs were associated with a mean BP reduction of 2.09 (95% CI 2.78-1.40) mmHg for systolic BP and 1.92 (95% CI 2.40-1.43) mmHg for diastolic BP and 1.27 (95% CI 2.34-0.20) mmHg for systolic BP and 1.11 (95% CI 1.82-0.41) mmHg for diastolic BP, respectively. The subgroups of patients who showed a greater response were those aged <60 years (systolic BP 2.93 mmHg), with uncontrolled BP at baseline (systolic BP 4.14 mmHg) and with severe oxygen desaturations (minimum arterial oxygen saturation measured by pulse oximetry <77%) at baseline (24-h systolic BP 7.57 mmHg). Although this meta-analysis shows that the expected reduction of BP by CPAP/MADs is modest, it identifies specific characteristics that may predict a pronounced benefit from CPAP in terms of BP control. These findings should be interpreted with caution; however, they are particularly important in identifying potential phenotypes associated with BP reduction in patients treated for OSA.
Published: 2020

20. Reboxetine plus Oxybutynin for Obstructed Sleep Apnea Treatment A 1-week Randomized, Placebo-controlled, Double-Blind Crossover Trial

Author: Perger, E, Montemurro, L, Rosa, D, Vicini, S, Marconi, M, Zanotti, L, Meriggi, P, Azarbarzin, A, Sands, S, Wellman, A, Lombardi, C, Parati, G, Perger, Elisa, Montemurro, Luigi Taranto, Rosa, Debora, Vicini, Stefano, Marconi, Mariapaola, Zanotti, Lucia, Meriggi, Paolo, Azarbarzin, Ali, Sands, Scott A, Wellman, Andrew, Lombardi, Carolina, Parati, Gianfranco, Perger, E, Montemurro, L, Rosa, D, Vicini, S, Marconi, M, Zanotti, L, Meriggi, P, Azarbarzin, A, Sands, S, Wellman, A, Lombardi, C, Parati, G, Perger, Elisa, Montemurro, Luigi Taranto, Rosa, Debora, Vicini, Stefano, Marconi, Mariapaola, Zanotti, Lucia, Meriggi, Paolo, Azarbarzin, Ali, Sands, Scott A, Wellman, Andrew, Lombardi, Carolina, and Parati, Gianfranco
Abstract: Background: The recent discovery that a combination of noradrenergic and antimuscarinic drugs improved upper airway muscle function during sleep and reduced OSA severity has revitalized interest in pharmacologic therapies for OSA. Research Question: Would 1 week of reboxetine plus oxybutynin (Reb-Oxy) be effective on OSA severity? Study Design and Methods: A randomized, placebo-controlled, double-blind, crossover trial was performed comparing 4 mg reboxetine plus 5 mg oxybutynin (Reb-Oxy) vs placebo in patients with OSA. After a baseline in-laboratory polysomnogram (PSG), patients underwent PSGs after 7 nights of Reb-Oxy and 7 nights of placebo to compare apnea-hypopnea index (AHI), which was the primary outcome. Response rate was based on the percentage of subjects with a ≥ 50% reduction in AHI from baseline. Secondary outcomes included Epworth Sleepiness Scale (ESS) score and psychomotor vigilance test (PVT) values. Home oximetry evaluated overnight oxygen desaturation index (ODI) throughout treatment. Results: Sixteen subjects aged 57 [51-61] years (median [interquartile range]) with a BMI of 30 [26-36] kg/m2 completed the study. Reb-Oxy lowered AHI from 49 [35-57] events per hour at baseline to 18 [13-21] events per hour (59% median reduction) compared with 39 [29-48] events per hour (6% median reduction) with placebo (P <.001). Response rate for Reb-Oxy was 81% vs 13% for placebo (P <.001). Although ESS scores were not significantly lowered, PVT median reaction time decreased from 250 [239-312] ms at baseline to 223 [172-244] ms on Reb-Oxy vs 264 [217-284] ms on placebo (P <.001). Home oximetry illustrated acute and sustained improvement in the oxygen desaturation index on Reb-Oxy vs placebo. Interpretation: The administration of Reb-Oxy greatly decreased OSA severity and increased vigilance. These results highlight potential possibilities for pharmacologic treatment of OSA. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04449133; URL: www.cl
Published: 2022

21. Right heart chambers geometry and function in patients with the atrial and the ventricular phenotypes of functional tricuspid regurgitation

Author: Florescu, D, Muraru, D, Florescu, C, Volpato, V, Caravita, S, Perger, E, Bălșeanu, T, Parati, G, Badano, L, Florescu, Diana R, Muraru, Denisa, Florescu, Cristina, Volpato, Valentina, Caravita, Sergio, Perger, Elisa, Bălșeanu, Tudor A, Parati, Gianfranco, Badano, Luigi, Florescu, D, Muraru, D, Florescu, C, Volpato, V, Caravita, S, Perger, E, Bălșeanu, T, Parati, G, Badano, L, Florescu, Diana R, Muraru, Denisa, Florescu, Cristina, Volpato, Valentina, Caravita, Sergio, Perger, Elisa, Bălșeanu, Tudor A, Parati, Gianfranco, and Badano, Luigi
Abstract: AIMS: Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of functional tricuspid regurgitation (FTR) associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the right ventricle, right atrium, and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Accordingly, we sought to: (i) study the geometry and function of the right ventricle, right atrium, and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and (ii) compare them with those found in V-FTR. METHODS AND RESULTS: We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Severity of FTR was similar in A-FTR and V-FTR patients. Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (P < 0.001 for all). The right atrium was significantly enlarged in both A-FTR and V-FTR compared to controls (P < 0.001, Z-scores > 2), with similar right atrial (RA) maximum volume (RAVmax) between A-FTR and V-FTR (P = 0.2). Whereas, the RA minimum volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (P = 0.001). CONCLUSION: Despite similar degrees of FTR and RAVmax size, A-FTR patients show larger RAVmin and smaller TA areas than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional right ventricle than A-FTR patients.
Published: 2022

22. Predictors of 1-year compliance with adaptive servoventilation in patients with heart failure and sleep disordered breathing: preliminary data from the ADVENT-HF trial

Author: Perger, E, Lyons, O, Inami, T, Smith, S, Floras, J, Logan, A, Bradley, T, Perger E., Lyons O. D., Inami T., Smith S., Floras J. S., Logan A. G., Bradley T. D., Perger, E, Lyons, O, Inami, T, Smith, S, Floras, J, Logan, A, Bradley, T, Perger E., Lyons O. D., Inami T., Smith S., Floras J. S., Logan A. G., and Bradley T. D.
Published: 2019

23. Obstructive sleep apnea and cardiovascular disease

Author: Perger, E, Gonzaga-Carvalho, C, Inami, T, Ryan, C, Lyons, O, Perger E., Gonzaga-Carvalho C., Inami T., Ryan C. M., Lyons O. D., Perger, E, Gonzaga-Carvalho, C, Inami, T, Ryan, C, Lyons, O, Perger E., Gonzaga-Carvalho C., Inami T., Ryan C. M., and Lyons O. D.
Published: 2019

24. Postural respiratory-related cortical activation and rostral fluid shift in awake healthy humans

Author: Launois, C, Perger, E, Attali, V, Nierat, M, Raux, M, Arnulf, I, Similowski, T, Redolfi, S, Launois C., Perger E., Attali V., Nierat M. -C., Raux M., Arnulf I., Similowski T., Redolfi S., Launois, C, Perger, E, Attali, V, Nierat, M, Raux, M, Arnulf, I, Similowski, T, Redolfi, S, Launois C., Perger E., Attali V., Nierat M. -C., Raux M., Arnulf I., Similowski T., and Redolfi S.
Abstract: New Findings: What is the central question of this study? Moving to supine induces upper airway modifications and a fluid shift to the neck, which represent inspiratory load that predisposes to upper airway collapse. Is there cortical participation in the response to the load induced by transition to a supine posture in awake healthy subjects? What is the main finding and its importance? Moving to supine induces transient cortical activation in awake healthy subjects, with greater fluid shift, supporting possible cortical participation in the response to upper airway load induced by transition to a supine posture. Our findings open new perspectives in the understanding of the pathogenesis of obstructive sleep apnoea. Abstract: Moving from sitting upright to lying supine causes anatomical modifications and a fluid shift to the neck, which represent inspiratory loads that predispose to upper airway collapse. The pre-inspiratory potential (PIP) corresponds to the cortical activity observed during inspiratory load. In the sitting position during wakefulness, some obstructive sleep apnoea patients exhibit PIP, probably in relationship to upper airway abnormalities. The aim of this study was to investigate whether moving to the supine position induces respiratory-related cortical activation (PIP) in awake healthy subjects. The ECG was analysed to detect PIP, and EMG activity of the genioglossus muscle and ventilation were measured in the sitting position, immediately after moving to the supine position, and during application of leg positive pressure in the supine position to promote fluid shift, which was measured by bioelectrical impedance. Twenty-four subjects were included. From sitting to lying, PIP prevalence increased from 1/24 to 11/24 (P = 0.002), and ventilation decreased with no change in genioglossus activity. The fluid shift from sitting to supine was higher in the subjects exhibiting PIP while supine compared with the subjects without PIP
Published: 2019

25. Hypertension and atrial fibrillation in obstructive sleep apnea: Is it a menopause issue?

Author: Perger, E, Pengo, M, Lombardi, C, Perger E., Pengo M. F., Lombardi C., Perger, E, Pengo, M, Lombardi, C, Perger E., Pengo M. F., and Lombardi C.
Abstract: Obstructive sleep apnoea (OSA) is a common disorder, in which loss of pharyngeal dilator muscle tone during sleep causes recurrent collapse of the upper airway and temporary cessation of breathing. Repeated apneas and hypopneas lead to cycles of intermittent hypoxia/hypercapnia, increased negative intrathoracic pressure and arousals from sleep. These consequences of OSA are associated with a cascade of cardiovascular and neurohumoral consequences, including sympathetic nervous system hyperactivity, raised heart rate variability, increases in blood pressure, myocardial wall stress, oxidative stress, systemic inflammation, platelet aggregation and impaired vascular endothelial function, which contribute, in turn, to increased cardiovascular risk and, in particular, to the development of chronic systemic arterial hypertension and arrhythmias, especially atrial fibrillation (AF). Given that the prevalence of OSA is modified by age and gender, OSA-related cardiovascular diseases may also be affected by the same factors. This review focuses on the potential role of OSA in systemic arterial hypertension and AF, and discusses the most interesting studies on age and gender as predisposing factors.
Published: 2019

26. Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure

Author: Inami, T, Kasai, T, Yumino, D, Perger, E, Alshaer, H, Hummel, R, Lyons, O, Floras, J, Bradley, T, Inami T., Kasai T., Yumino D., Perger E., Alshaer H., Hummel R., Lyons O. D., Floras J. S., Bradley T. D., Inami, T, Kasai, T, Yumino, D, Perger, E, Alshaer, H, Hummel, R, Lyons, O, Floras, J, Bradley, T, Inami T., Kasai T., Yumino D., Perger E., Alshaer H., Hummel R., Lyons O. D., Floras J. S., and Bradley T. D.
Abstract: Study Objectives In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), stroke volume (SV) falls during hyperpnea of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). We have identified two distinct patterns of hyperpnea: Positive, in which end-expiratory lung volume (EELV) remains at or above functional residual capacity (FRC), and negative, in which EELV falls below FRC. The increase in expiratory intrathoracic pressure generated by the latter should have effects on the heart analogous to external chest compression. To test the hypotheses that in HFrEF patients, CSR-CSA with the negative pattern has an auto-resuscitation effect such that compared with the positive pattern, it is associated with a smaller fall in SV and a smaller increase in cardiac workload (product of heart rate and systolic blood pressure). Methods In 15 consecutive HFrEF patients with CSR-CSA during polysomnography, hemodynamic data derived from digital photoplethysmography during positive and negative hyperpneas were compared. Results Compared to the positive, negative hyperpneas were accompanied by reductions in the maximum and mean relative fall in SV of 30% (p = 0.002) and 10% (p = 0.031), respectively, and by reductions in the degree of increases in heart rate and rate pressure product during hyperpnea of 46% (p < 0.001) and 13% (p = 0.007), respectively. Conclusions Our findings suggest the novel concept that the negative pattern of CSR-CSA may constitute a form of auto-resuscitation that acts as a compensatory mechanism to maintain SV in patients with severe HF.
Published: 2019

27. Menopause and Sleep Apnea

Author: Perger, E, Mattaliano, P, Lombardi, C, Perger E., Mattaliano P., Lombardi C., Perger, E, Mattaliano, P, Lombardi, C, Perger E., Mattaliano P., and Lombardi C.
Abstract: Obstructive sleep apnea (OSA) is a chronic and common adult disorder characterized by recurrent episodes of upper-airway obstruction and reopening during sleep. OSA is associated with intermittent hypoxia, sympathetic overactivity, oxidative stress and high cardiovascular mortality and morbidity. It is known to be more common in men than women, partly due to differences in anatomy and functional respiratory components. There are also gender differences in reported symptoms, leading to potential under-diagnosis in females. This gender difference tends to decrease after menopause, demonstrating a role of menopausal status itself in OSA phenotypes. Aging, fat mass distribution, sex hormones and upper-airway collapsibility are postulated to play a major role in these findings. This review focuses on the most recent studies exploring gender differences in the prevalence, pathogenesis and clinical features of OSA. It discusses the role of menopause in this, and explore the underlying pathophysiological mechanisms.
Published: 2019

28. The influence of drug therapy for obstructive sleep apnoea on couple life. Qualitative study grounded theory

Author: Rosa, D, primary, Amigoni, C, additional, Villa, G, additional, Albanesi, B, additional, Bonetti, L, additional, Lombardi, C, additional, Perger, E, additional, and Parati, G, additional
Published: 2021
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29. Breath-holding as a novel approach to risk stratification in COVID-19.

Author: Messineo L., Perger E., Corda L., Joosten S.A., Fanfulla F., Pedroni L., Terrill P.I., Lombardi C., Wellman A., Hamilton G.S., Malhotra A., Vailati G., Parati G., Sands S.A., Messineo L., Perger E., Corda L., Joosten S.A., Fanfulla F., Pedroni L., Terrill P.I., Lombardi C., Wellman A., Hamilton G.S., Malhotra A., Vailati G., Parati G., and Sands S.A.
Abstract: Background: Despite considerable progress, it remains unclear why some patients admitted for COVID-19 develop adverse outcomes while others recover spontaneously. Clues may lie with the predisposition to hypoxemia or unexpected absence of dyspnea ('silent hypoxemia') in some patients who later develop respiratory failure. Using a recently-validated breath-holding technique, we sought to test the hypothesis that gas exchange and ventilatory control deficits observed at admission are associated with subsequent adverse COVID-19 outcomes (composite primary outcome: non-invasive ventilatory support, intensive care admission, or death). Method(s): Patients with COVID-19 (N = 50) performed breath-holds to obtain measurements reflecting the predisposition to oxygen desaturation (mean desaturation after 20-s) and reduced chemosensitivity to hypoxic-hypercapnia (including maximal breath-hold duration). Associations with the primary composite outcome were modeled adjusting for baseline oxygen saturation, obesity, sex, age, and prior cardiovascular disease. Healthy controls (N = 23) provided a normative comparison. Result(s): The adverse composite outcome (observed in N = 11/50) was associated with breath-holding measures at admission (likelihood ratio test, p = 0.020); specifically, greater mean desaturation (12-fold greater odds of adverse composite outcome with 4% compared with 2% desaturation, p = 0.002) and greater maximal breath-holding duration (2.7-fold greater odds per 10-s increase, p = 0.036). COVID-19 patients who did not develop the adverse composite outcome had similar mean desaturation to healthy controls. Conclusion(s): Breath-holding offers a novel method to identify patients with high risk of respiratory failure in COVID-19. Greater breath-hold induced desaturation (gas exchange deficit) and greater breath-holding tolerance (ventilatory control deficit) may be independent harbingers of progression to severe disease.Copyright © 2021, The Author(s).
Published: 2021

30. Sleep-disordered breathing among hospitalized patients with COVID-19

Author: Perger, E, Soranna, D, Pengo, M, Meriggi, P, Lombardi, C, Parati, G, Perger, E, Soranna, D, Pengo, M, Meriggi, P, Lombardi, C, and Parati, G
Published: 2021

31. Investigating the link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms

Author: Pini, L, Peroni, M, Zanotti, C, Pini, A, Bossoni, E, Giordani, J, Bargagli, E, Perger, E, Ferrarotti, I, Vizzardi, E, Tiberio, L, Bonardelli, S, Tantucci, C, Pini, Laura, Peroni, Michele, Zanotti, Camilla, Pini, Alessandro, Bossoni, Erika, Giordani, Jordan, Bargagli, Elena, Perger, Elisa, Ferrarotti, Ilaria, Vizzardi, Enrico, Tiberio, Laura, Bonardelli, Stefano, Tantucci, Claudio, Pini, L, Peroni, M, Zanotti, C, Pini, A, Bossoni, E, Giordani, J, Bargagli, E, Perger, E, Ferrarotti, I, Vizzardi, E, Tiberio, L, Bonardelli, S, Tantucci, C, Pini, Laura, Peroni, Michele, Zanotti, Camilla, Pini, Alessandro, Bossoni, Erika, Giordani, Jordan, Bargagli, Elena, Perger, Elisa, Ferrarotti, Ilaria, Vizzardi, Enrico, Tiberio, Laura, Bonardelli, Stefano, and Tantucci, Claudio
Abstract: Objectives: Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present. AATD could be a reasonable risk factor for AAA because it is related to protease/antiprotease imbalance and enhanced ECM degradation of the vessel wall. Methods: We performed genotyping of 138 patients hospitalized in the Vascular Surgery Division of the ASST-Spedali Civili di Brescia, Italy, for non-traumatic rupture of AAA. The second purpose was to observe the distribution of main non-genetic risk factors for AAA between patients with and without AATD. Results: Out of 138 patients, 22 were found with AATD: 16 MS, 1 SS, 3 MZ, and 2 with a new rare AAT variant. When compared to the general Italian population, our cohort's frequency of deficient S allele was significantly higher (7.8 vs 2.2% respectively, P<0.01), whereas the deficient Z allele was similar (1.1 vs 1.3% respectively, P>0.05). Although we found no differences in age, gender, hypertension, diabetes, and smoke habits between AAA patients with and without AATD, hyperlipidemia was significantly less frequent in patients with AATD (46.4 vs 12.5% respectively, P<0.05). Conclusions: In our AAA patients' cohort, the S allele frequency was higher than in the general Italian population. Our results support the hypothesis that AATD might be a risk factor for AAA.
Published: 2021

32. Upper airway muscles: influence on obstructive sleep apnoea pathophysiology and pharmacological and technical treatment options

Author: Perger, E, Taranto-Montemurro, L, Perger, Elisa, Taranto-Montemurro, Luigi, Perger, E, Taranto-Montemurro, L, Perger, Elisa, and Taranto-Montemurro, Luigi
Abstract: Purpose of review: Obstructive sleep apnoea (OSA) is highly prevalent with numerous deleterious effects on neurocognitive and cardiovascular health. It is characterized by collapse of the upper airway during sleep, due to the decrease in both basal and compensatory UA muscle activities. However, the leading treatment, continuous positive airway pressure, is often poorly tolerated. This review presents latest works focusing on novel interventions targeting upper airway muscles to alleviate OSA severity. Recent findings: In the last years, researchers have focused on the development of alternative treatment strategies targeting UA muscle activation, including pharmacological and nonpharmacological interventions. Summary: Among the nonpharmacological treatments, hypoglossal nerve stimulation aims to increase upper airway muscle phasic activity during sleep through electrical stimulation, while myofunctional therapy improves the activity and coordination of upper airway dilator muscles.Regarding OSA pharmacotherapy, recent findings strongly suggest that selective norepinephrine reuptake inhibitors such as atomoxetine and reboxetine, when administered with antimuscarinics such as oxybutynin, can alleviate OSA in most patients increasing pharyngeal dilator muscles activity during sleep. New combinations of norepinephrine reuptake inhibitors and antimuscarinics have further been explored with variable success and animal models showed that leptin, thyrothropin releasing hormone analogues and gene therapy hold potential for the future of OSA pharmacotherapy.
Published: 2021

33. Improving CPAP Adherence in Adults With Obstructive Sleep Apnea Syndrome: A Scoping Review of Motivational Interventions

Author: Rapelli, Giada, Pietrabissa, Giada, Manzoni, G. M., Bastoni, I., Scarpina, F., Tovaglieri, I., Perger, E., Garbarino, S., Fanari, P., Lombardi, C., Castelnuovo, Gianluca, Rapelli G. (ORCID:0000-0002-6457-2169), Pietrabissa G. (ORCID:0000-0002-5911-5748), Castelnuovo G. (ORCID:0000-0003-2633-9822), Rapelli, Giada, Pietrabissa, Giada, Manzoni, G. M., Bastoni, I., Scarpina, F., Tovaglieri, I., Perger, E., Garbarino, S., Fanari, P., Lombardi, C., Castelnuovo, Gianluca, Rapelli G. (ORCID:0000-0002-6457-2169), Pietrabissa G. (ORCID:0000-0002-5911-5748), and Castelnuovo G. (ORCID:0000-0003-2633-9822)
Abstract: Objective: This scoping review aims to provide an accessible summary of available evidence on the efficacy of motivational interventions to increase adherence to Continuous Positive Airway Pressure (CPAP) among patients with Obstructive Sleep Apnea Syndrome (OSAS) and of their specific aspects and strategies by assessing adherence measures. Methods: A literature search was performed in PubMed, Scopus, Medline, PsycINFO, and Web of Science databases using the concepts of “obstructive sleep apnea syndrome,” “continuous positive airway pressure,” “motivational intervention,” and “adherence.” Rigorous inclusion criteria and screening by at least two reviewers were applied. Data were extracted to address the review aims and were presented as a narrative synthesis. Results: Search for databases produced 11 randomized controlled trials, all including naïve CPAP users. Findings showed that motivational interventions were more effective than usual care and educational programs in increasing adherence to CPAP, despite results were not always maintained over time across studies. Discussion: To our knowledge, this is the first scoping review of the literature aimed to explore the characteristics and impact of motivational interventions to promote adherence to CPAP in patients with OSAS. More research providing a detailed description of motivational strategies, and testing of their association with positive treatment outcomes via both direct and indirect measures are needed to increase awareness on active mechanisms of change.
Published: 2021

34. Reboxetine Plus Oxybutynin for Obstructed Sleep Apnea Treatment

Author: Perger, E., primary, Taranto Montemurro, L., additional, Rosa, D., additional, Vicini, S., additional, Marconi, M., additional, Zanotti, L., additional, Meriggi, P., additional, Azarbarzin, A., additional, Sands, S.A., additional, Wellman, A., additional, Lombardi, C., additional, and Parati, G., additional
Published: 2021
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35. Targeting volume overload and overnight rostral fluid shift: A new perspective to treat sleep apnea

Author: Perger, E, Jutant, E, Redolfi, S, Perger E., Jutant E. -M., Redolfi S., Perger, E, Jutant, E, Redolfi, S, Perger E., Jutant E. -M., and Redolfi S.
Abstract: Sleep apnea is a common condition associated with increased morbidity and mortality. Continuous positive airway pressure and oral appliances are efficient for treating sleep apnea; however, they are often poorly tolerated. Therefore, alternative therapies are needed. Overnight rostral fluid shift has been implicated in the pathogenesis of sleep apnea, particularly in conditions associated with fluid overload. Fluid shift predisposes to both obstructive and central sleep apnea, with the type of sleep apnea being related to whether the fluid shifts from the legs into the neck or chest, respectively. The amount of fluid that shifts from the legs to the upper part of the body at night is correlated with the severity of sleep apnea. As a result of this observation, it has been suggested that the prevention of overnight fluid shift may reduce sleep apnea severity. It has recently been shown that interventions targeting fluid overload and daytime fluid accumulation in the legs consistently attenuate nocturnal fluid shift and sleep apnea, as greater reductions in fluid shift are correlated with greater reductions in sleep apnea severity. This review will focus on interventions that counteract fluid shift, such as diuretics, ultrafiltration/dialysis, physical activity, compression stockings and salt/fluid restriction, which have been shown to have efficacy in reducing sleep apnea severity.
Published: 2018

36. Heart rate variability responses of individuals with and without saline-induced obstructive sleep apnea

Author: Vena, D, Bradley, T, Millar, P, Floras, J, Rubianto, J, Gavrilovic, B, Perger, E, Yadollahi, A, Vena D., Bradley T. D., Millar P. J., Floras J. S., Rubianto J., Gavrilovic B., Perger E., Yadollahi A., Vena, D, Bradley, T, Millar, P, Floras, J, Rubianto, J, Gavrilovic, B, Perger, E, Yadollahi, A, Vena D., Bradley T. D., Millar P. J., Floras J. S., Rubianto J., Gavrilovic B., Perger E., and Yadollahi A.
Abstract: Study Objectives: Postoperative development of obstructive sleep apnea (OSA) has been attributed to the fluid overloaded state of patients during the postoperative period. In this context, alterations in cardiac autonomic regulation caused by OSA may explain the increased postoperative risk for adverse cardiovascular events. This study tests the hypothesis that individuals with fluid overload-induced OSA will experience autonomic dysregulation, compared to those without fluid overload-induced OSA. Methods: Twenty-one normotensive, nonobese (mean body mass index 24.5 kg/m2) males (mean age 37 years) underwent a sleep study. Participants were randomly assigned to infusion with saline during sleep either at the minimum rate (control) or as a bolus of 22 mL/kg body weight (intervention). Participants were blinded to the intervention and crossed over to the other study arm after 1 week. Measures of heart rate variability were calculated from electrocardiography recordings presaline and postsaline infusion in the intervention arm. Heart rate variability measures computed were: standard deviation of the RR interval; root mean square of successive differences; low-frequency, high-frequency, and total power; and the ratio of low-frequency to highfrequency power. Results: Although presaline infusion values were similar, postsaline infusion values of the standard deviation of the RR interval and high-frequency power were lower in the group whose apnea-hypopnea index increased in response to saline infusion, compared to the group whose apnea-hypopnea index did not increase in response to saline infusion (P <.05 for both). Conclusions: Fluid overload-induced OSA is accompanied by a reduction in heart rate variability, consistent with vagal withdrawal. Future work should explore autonomic dysregulation in the postoperative period and its association with adverse events.
Published: 2018

37. Obstructive sleep apnea and chronic kidney disease

Author: Lin, C, Perger, E, Lyons, O, Lin C. -H., Perger E., Lyons O. D., Lin, C, Perger, E, Lyons, O, Lin C. -H., Perger E., and Lyons O. D.
Abstract: PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is highly prevalent in patients with chronic kidney disease (CKD). The relationship between OSA and CKD is likely to be bi-directional. On one hand, the presence of OSA leads to intermittent hypoxia, sympathetic nervous system activity, and hypertension, all of which may have deleterious effects on kidney function. On the other hand, in patients with end-stage renal disease (ESRD), intensification of renal replacement therapy has been shown to attenuate sleep apnea severity, suggesting that the renal disease itself contributes to the pathogenesis of OSA. The present review describes our current understanding of the bi-directional relationship between OSA and CKD. RECENT FINDINGS: Studies suggest that the presence of OSA and nocturnal hypoxia may lead to worsening of kidney function. One potential mechanism is activation of the renin-angiotensin system by OSA, an effect which may be attenuated by CPAP therapy. In ESRD, fluid overload plays an important role in the pathogenesis of OSA and fluid removal by ultrafiltration leads to marked improvements in sleep apnea severity. SUMMARY: OSA is associated with accelerated loss of kidney function. In patients with ESRD, fluid overload plays an important role in the pathogenesis of OSA.
Published: 2018

38. Evening sock marks as an adjunct to the clinical prediction of obstructive sleep apnea

Author: Perger, E, Badarani, O, Philippe, C, Rivals, I, Arnulf, I, Similowski, T, Redolfi, S, Perger, Elisa, Badarani, Oumama, Philippe, Carole, Rivals, Isabelle, Arnulf, Isabelle, Similowski, Thomas, Redolfi, Stefania, Perger, E, Badarani, O, Philippe, C, Rivals, I, Arnulf, I, Similowski, T, Redolfi, S, Perger, Elisa, Badarani, Oumama, Philippe, Carole, Rivals, Isabelle, Arnulf, Isabelle, Similowski, Thomas, and Redolfi, Stefania
Abstract: Study objectives: Fluid overload shifting from the legs to the upper airway during sleep promotes obstructive sleep apnea (OSA) and interventions targeting fluid attenuate OSA. Fluid shift has been previously measured by bioelectrical impedance, a complex and time-consuming technique not applicable in the daily clinical settings. The aim of this study is to evaluate the presence of clinically detectable fluid overload and shift and its association with OSA. Methods: Patients undergoing sleep study for suspected OSA were asked to report the presence of 11 signs/symptoms associated to excessive accumulation of fluid in different parts of the body at different times of the day. Results: Among 392 patients (male: 53%, median [interquartile range] age: 56 years [1], body mass index, BMI: 29 kg/m2 [2]) included in the study, 135 (34%) had moderate-to-severe OSA (apnea hypopnea index, AHI ≥ 15). Daytime fluid accumulation and nocturnal fluid shift, clinically detectable by patient-reported “evening sock marks,” “heavy legs during the day,” and “morning stuffed nose,” were prevalent in the entire population (46%, 43%, and 33%, respectively). In multivariate analysis, evening sock marks was an independent correlate of having an AHI ≥ 15, together with male sex, older age, and self-reported snoring and apneas. Conclusions: Clinically detectable fluid overload and shift are prevalent in patients addressed for suspected OSA, and evening sock marks, a marker for leg swelling, is an independent correlate of moderate-to-severe OSA. This sign might contribute to OSA diagnosis and identification of patients likely to be treated by interventions targeting fluid overload and shift.
Published: 2020

39. The effect of fluid overload on sleep apnoea severity in haemodialysis patients

Author: Lyons, O, Inami, T, Perger, E, Yadollahi, A, Chan, C, Bradley, T, Lyons O. D., Inami T., Perger E., Yadollahi A., Chan C. T., Bradley T. D., Lyons, O, Inami, T, Perger, E, Yadollahi, A, Chan, C, Bradley, T, Lyons O. D., Inami T., Perger E., Yadollahi A., Chan C. T., and Bradley T. D.
Abstract: As in heart failure, obstructive and central sleep apnoea (OSA and CSA, respectively) are common in end-stage renal disease. Fluid overload characterises end-stage renal disease and heart failure, and in heart failure plays a role in the pathogenesis of OSA and CSA. We postulated that in end-stage renal disease patients, those with sleep apnoea would have greater fluid volume overload than those without. End-stage renal disease patients on thrice-weekly haemodialysis underwent overnight polysomnography on a nondialysis day to determine their apnoea-hypopnoea index (AHI). Extracellular fluid volume of the total body, neck, thorax and right leg were measured using bioelectrical impedance. 28 patients had an AHI ≥15 (sleep apnoea group; OSA:CSA 21:7) and 12 had an AHI <15 (no sleep apnoea group). Total body extracellular fluid volume was 2.6 L greater in the sleep apnoea group than in the no sleep apnoea group (p=0.006). Neck, thorax, and leg fluid volumes were also greater in the sleep apnoea than the no sleep apnoea group ( p<0.05), despite no difference in body mass index (p=0.165). These findings support a role for fluid overload in the pathogenesis of both OSA and CSA in end-stage renal disease.
Published: 2017

40. Cardiac Sympathetic Hyperactivity in Patients with Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea

Author: Taranto-Montemurro, L, Messineo, L, Perger, E, Salameh, M, Pini, L, Corda, L, Ferliga, M, Tantucci, C, Taranto-Montemurro L, Messineo L, Perger E, Salameh M, Pini L, Corda L, Ferliga M, Tantucci C., Taranto-Montemurro, L, Messineo, L, Perger, E, Salameh, M, Pini, L, Corda, L, Ferliga, M, Tantucci, C, Taranto-Montemurro L, Messineo L, Perger E, Salameh M, Pini L, Corda L, Ferliga M, and Tantucci C.
Abstract: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) coexist in 0.5–1% of the general population. Both OSA and COPD are associated with increased sympathetic nervous activity, and patients affected by both disorders have higher risk for increased morbidity and mortality as compared with patients with COPD or OSA alone. We tested the hypothesis that patients with COPD and OSA (Overlap syndrome) have higher sympathetic and lower parasympathetic modulation of heart rate variability (HRV) in comparison with patients suffering from COPD or OSA alone. HRV indices in the frequency domain were evaluated from daytime electrocardiographic recordings in 14 patients with both severe OSA (apnea–hypopnea index ≥ 30) and mild-to-moderate COPD and compared with those with OSA (n = 24) or COPD (n = 16) alone. We found that, in the Overlap syndrome group, high-frequency (HF, 0.4–0.15 Hz) power was significantly lower (0.18 nu vs 0.34 nu in OSA and 0.44 nu in COPD patients, p < 0.01) and low-frequency (LF, 0.15–0.05 Hz) power was significantly greater (0.82 nu vs 0.66 nu in OSA and 0.57 nu in COPD patients, p < 0.01) compared with COPD and OSA groups. Patients with both OSA and COPD had higher LF/HF ratio as compared with patients in OSA and COPD groups (4.5 [5.9] vs 1.9 [2.6] and 1.3 [1.3], respectively, p < 0.01). For the Overlap syndrome group, there was a significant direct relationship between LF/HF ratio and residual volume (r2 = 0.62, p = 0.007). These findings show that patients with both OSA and COPD have higher sympathetic modulation of heart rate compared with those with OSA or COPD alone. Furthermore, the findings provide a potential mechanism for the increased morbidity and mortality reported in patients suffering from both disorders, suggesting new therapeutic perspectives in Overlap syndrome.
Published: 2016

41. OSA Phenotypic Traits in Morbid Obese Patients with Isolated Sleep Hypoventilation

Author: Perger, E., primary, Taranto Montemurro, L., additional, Sands, S.A., additional, Aron-Wisnewsky, J., additional, Arnulf, I., additional, Oppert, J.-M., additional, Wellman, D.A., additional, Similowski, T., additional, and Redolfi, S., additional
Published: 2019
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42. Effect of CPAP on Arrhythmias in Two OSA Patients

Author: Perger, E., primary, Philippe, C., additional, Arnulf, I., additional, and Redolfi, S., additional
Published: 2019
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43. Syndrome d’apnées obstructives du sommeil dans l’insuffisance veineuse en relation avec la rétention hydrique

Author: Perger, E., primary, Blaise, S., additional, Vermorel, C., additional, Bodge, G., additional, Pepin, J.L., additional, Redolfi, S., additional, and Bosson, J.L., additional
Published: 2018
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44. Évaluation des troubles respiratoires du sommeil chez patients avec une obésité morbide

Author: Perger, E., primary, Aron-Wisnewsky, J., additional, Philippe, C., additional, Arnulf, I., additional, Oppert, J.M., additional, and Redolfi, S., additional
Published: 2018
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45. Prédicteurs de l’observance à court et long-terme de la ventilation auto-asservie dans l’étude Advent-HF

Author: Perger, E., primary, Lyons, O., additional, Inami, T., additional, Smith, S., additional, Floras, J., additional, Logan, A., additional, Redolfi, S., additional, and Bradley, D., additional
Published: 2018
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46. Distinct patterns of hyperpnea during cheyne-stokes respiration: Implication for cardiac function in patients with heart failure

Author: Perger, E, Inami, T, Lyons, O, Alshaer, H, Smith, S, Floras, J, Logan, A, Arzt, M, Cantolla, J, Delgado, D, Fitzpatrick, M, Fleetham, J, Kasai, T, Kimoff, R, Leung, R, Filho, G, Mayer, P, Mielniczuk, L, Morrison, D, Parati, G, Parthasarathy, S, Redolfi, S, Ryan, C, Series, F, Tomlinson, G, Woo, A, Bradley, T, Perger, Elisa, Inami, Toru, Lyons, Owen D., Alshaer, Hisham, Smith, Stephanie, Floras, John S., Logan, Alexander G., Arzt, Michael, Cantolla, Joaquin Duran, Delgado, Diego, Fitzpatrick, Michael, Fleetham, John, Kasai, Takatoshi, Kimoff, R. John, Leung, Richard S. T., Filho, Geraldo Lorenzi, Mayer, Pierre, Mielniczuk, Lisa, Morrison, Debra L., Parati, Gianfranco, Parthasarathy, Sairam, Redolfi, Stefania, Ryan, Clodagh M., Series, Frederic, Tomlinson, George A., Woo, Anna, Bradley, T. Douglas, Perger, E, Inami, T, Lyons, O, Alshaer, H, Smith, S, Floras, J, Logan, A, Arzt, M, Cantolla, J, Delgado, D, Fitzpatrick, M, Fleetham, J, Kasai, T, Kimoff, R, Leung, R, Filho, G, Mayer, P, Mielniczuk, L, Morrison, D, Parati, G, Parthasarathy, S, Redolfi, S, Ryan, C, Series, F, Tomlinson, G, Woo, A, Bradley, T, Perger, Elisa, Inami, Toru, Lyons, Owen D., Alshaer, Hisham, Smith, Stephanie, Floras, John S., Logan, Alexander G., Arzt, Michael, Cantolla, Joaquin Duran, Delgado, Diego, Fitzpatrick, Michael, Fleetham, John, Kasai, Takatoshi, Kimoff, R. John, Leung, Richard S. T., Filho, Geraldo Lorenzi, Mayer, Pierre, Mielniczuk, Lisa, Morrison, Debra L., Parati, Gianfranco, Parthasarathy, Sairam, Redolfi, Stefania, Ryan, Clodagh M., Series, Frederic, Tomlinson, George A., Woo, Anna, and Bradley, T. Douglas
Abstract: Study Objectives: In heart failure (HF), we observed two patterns of hyperpnea during Cheyne-Stokes respiration with central sleep apnea (CSR-CSA): a positive pattern where end-expiratory lung volume remains at or above functional residual capacity, and a negative pattern where it falls below functional residual capacity. We hypothesized the negative pattern is associated with worse HF. Methods: Patients with HF underwent polysomnography. During CSR-CSA, hyperpnea, apnea-hyperpnea cycle, and lung to finger circulation times (LFCT) were measured. Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentration and left ventricular ejection fraction (LVEF) were assessed. Results: Of 33 patients with CSR-CSA (31 men, mean age 68 years), 9 had a negative hyperpnea pattern. There was no difference in age, body mass index, and apnea-hypopnea index between groups. Patients with a negative pattern had longer hyperpnea time (39.5 Â± 6.4 versus 25.8 Â± 5.9 seconds, P < .01), longer cycle time (67.8 Â± 15.9 versus 51.7 Â± 9.9 seconds, P < .01), higher NT-proBNP concentrations (2740 [6769] versus 570 [864] pg/ml, P = .01), and worse New York Heart Association class (P = .02) than those with a positive pattern. LFCT and LVEF did not differ between groups. Conclusions: Patients with HF and a negative CSR-CSA pattern have evidence of worse cardiac function than those with a positive pattern. Greater positive expiratory pressure during hyperpnea is likely generated during the negative pattern and might support stroke volume in patients with worse cardiac function. Commentary: A commentary on this article appears in this issue on page 1227. Clinical Trial Registration: The trial is registered with Current Controlled Trials (www.controlled-trials.com; ISRCTN67500535) and Clinical Trials (www. clinicaltrials.gov; NCT01128816).
Published: 2017

47. Effects Of Varying Cheyne-Stokes Respiration Pattern On Stroke Volume In Patients With Heart Failure

Author: Perger, E, Inami, T, Lyons, O, Smith, S, Douglas Bradley, T, Elisa Perger, Toru Inami, Owen Lyons, Stephanie Smith, T. Douglas Bradley, Perger, E, Inami, T, Lyons, O, Smith, S, Douglas Bradley, T, Elisa Perger, Toru Inami, Owen Lyons, Stephanie Smith, and T. Douglas Bradley
Published: 2017

48. Varying patterns of hyperpnea during Cheyne-Stokes respiration in heart failure: Implication for cardiac function

Author: Perger, E, Inami, T, Lyons, O, Smith, S, Bradley, T, Perger, Elisa, Inami, Toru, Lyons, Owen, Smith, Stephanie, Bradley, T. Douglas, Perger, E, Inami, T, Lyons, O, Smith, S, Bradley, T, Perger, Elisa, Inami, Toru, Lyons, Owen, Smith, Stephanie, and Bradley, T. Douglas
Published: 2016

49. Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world

Author: Perger, Elisa, Baillieul, Sébastien, Esteve, François, Pichon, Aurélien, Bilo, Gzregorz, Soranna, Davide, Doutreleau, Stéphane, Savina, Yann, Ulliel-Roche, Mathilde, Brugniaux, Julien V., Stauffer, Emeric, Oberholzer, Laura, Howe, Connor, Hannco, Ivan, Lombardi, Carolina, Tamisier, Renaud, Pepin, Jean-Louis, Verges, Samuel, Parati, Gianfranco, Perger, E, Baillieul, S, Esteve, F, Pichon, A, Bilo, G, Soranna, D, Doutreleau, S, Savina, Y, Ulliel-Roche, M, Brugniaux, J, Stauffer, E, Oberholzer, L, Howe, C, Hannco, I, Lombardi, C, Tamisier, R, Pepin, J, Verges, S, and Parati, G
Subjects: Male, Blood Pressure, General Medicine, Altitude Sickness, Pulse Wave Analysis, Carotid Intima-Media Thickness, sleep disordered breathing, Cross-Sectional Studies, Sleep Apnea Syndromes, Chronic Disease, Hypertension, Quality of Life, Humans, blood pressure variability, chronic mountain sickne, Hypoxia, sleep apnoea, high-altitude
Abstract: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude. Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= −0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders. Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.
Published: 2022

50. SLEEP APNEA AND HYPOXIA: NEW THERAPEUTIC PROSPECTIVES

Author: PERGER, ELISA, Perger, E, PARATI, GIANFRANCO, and LOMBARDI, CAROLINA
Subjects: hypoxic burden, terapia dell'OSA, OSA treatment, MED/10 - MALATTIE DELL'APPARATO RESPIRATORIO, hypoxia, ipossia, carico ipossico, apnea del sonno, sleep apnea, disturbi del sonno, sleep disorder
Abstract: Un terzo della popolazione europea è affetta da apnee ostruttive del sonno (OSA), patologia che ha conseguenze negative su morbilità cardiovascolare e qualità della vita. L’OSA è caratterizzata da ripetuti episodi di collasso delle alte vie respiratorie che determinano ipossia intermittente, modifiche della pressione intratoracica e risvegli corticali. L’ipossia intermittente ha un ruolo chiave nel determinare le conseguenze cardiovascolari dei disturbi del respiro nel sonno e può sovrapporsi, peggiorandone la prognosi, a condizioni caratterizzate da ipossia tonica quali l’alta quota o le patologie respiratorie croniche o infettive, esacerbando lo stress ossidativo, l’angiogenesi e quindi l’attivazione del sistema nervoso simpatico con conseguenti incrementi della pressione arteriosa, della frequenza cardiaca e dell’infiammazione. Il trattamento gold standard per l’OSA è la terapia ventilatoria che risulta però non tollerata dalla metà dei pazienti che ne fanno uso. Nuove strategie terapeutiche sono pertanto auspicabili. Recentemente sono stati identificati specifici fattori fisiopatologici che contribuiscono allo sviluppo dell’OSA: un’elevata collassabilità delle vie aeree superiori, l’instabilità del sistema di controllo del respiro, una ridotta soglia di arousal ed una ridotta risposta compensatoria dei muscoli dilatatori della faringe. Quest’ultima è dovuta alla perdita di attività noradrenergica e aumento delle influenze muscariniche alle alte vie aeree. Il riconoscimento di questi tratti fisiopatologici ha permesso di ipotizzare e sviluppare nuove strategie terapeutiche per l’OSA. Obiettivo: Valutare l’efficacia della somministrazione per 1 settimana della combinazione di reboxetina (noradrenergico) ed ossibutinina (antimuscarinico) sul trattamento dell’OSA e dell’effetto dei farmaci sugli endotipi fisiopatologici. Metodi: E’ stato condotto uno studio randomizzato controllato cross-over in doppio cieco per comparare 4mg di reboxetina più 5mg di ossibutinina (reb-oxy) in pazienti con OSA. I pazienti sono stati sottoposti ad una polisonnografia basale (PSG), una dopo 7 notti di assunzione di reb-oxy ed una dopo 7 notti di assunzione di placebo per confrontare l’indice di apnea-ipopnea (AHI–outcome primario). Outcome secondari comprendevano il carico ipossico, modifiche degli endotipi, la variabilità della frequenza cardiaca, test di vigilanza. Risultati: Hanno completato lo studio 16 pazienti con età 57 [51-61] anni (mediana [range interquartilico]) ed indice di massa corporea 30 [26-36] kg/m2. Reb-oxy ha determinato una riduzione di AHI da 49 [35-57] eventi/h al basale a 18 [13-21] eventi/h (59% di riduzione mediana) e 39 [29-48] eventi/h (6% riduzione mediana) confrontato con il placebo (p
Published: 2023

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