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1. Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges

Author

Campo Ilaria, Kadija Zamir, Mariani Francesca, Paracchini Elena, Rodi Giuseppe, Mojoli Francesco, Braschi Antonio, and Luisetti Maurizio

Subjects
GM-CSF, Pulmonary alveolar proteinosis, WLL, Diseases of the respiratory system, RC705-779
Abstract

Abstract Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals and in distinct clinical forms: autoimmune (previously referred to as the idiopathic form, represents the vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) auto-antibodies; GMAbs), secondary (is a consequence of underlying disorders), congenital (caused by mutations in the genes encoding for the GM-CSF receptor), and PAP-like syndromes (disorders associated with surfactant gene mutations). The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole lung lavage (WLL) is the current standard treatment for PAP patients and although it is effective in the majority of cases, disease persistence is not an unusual outcome, even if disease is well controlled by WLL. In this paper we review the therapeutic strategies which have been proposed for the treatment of PAP patients and the progress which has been made in the understanding of the disease pathogenesis.

Published
2012
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2. In Lysinuric Protein Intolerance system y+L activity is defective in monocytes and in GM-CSF-differentiated macrophages

Author

Mariani Francesca, Rodi Giuseppe, Kadija Zamir, Gazzola Gian C, Bussolati Ovidio, Visigalli Rossana, Rotoli Bianca, Barilli Amelia, Ruzza Maria, Luisetti Maurizio, and Dall'Asta Valeria

Subjects
Medicine
Abstract

Abstract Background In the recessive aminoaciduria Lysinuric Protein Intolerance (LPI), mutations of SLC7A7/y+LAT1 impair system y+L transport activity for cationic amino acids. A severe complication of LPI is a form of Pulmonary Alveolar Proteinosis (PAP), in which alveolar spaces are filled with lipoproteinaceous material because of the impaired surfactant clearance by resident macrophages. The pathogenesis of LPI-associated PAP remains still obscure. The present study investigates for the first time the expression and function of y+LAT1 in monocytes and macrophages isolated from a patient affected by LPI-associated PAP. A comparison with mesenchymal cells from the same subject has been also performed. Methods Monocytes from peripheral blood were isolated from a 21-year-old patient with LPI. Alveolar macrophages and fibroblastic-like mesenchymal cells were obtained from a whole lung lavage (WLL) performed on the same patient. System y+L activity was determined measuring the 1-min uptake of [3H]-arginine under discriminating conditions. Gene expression was evaluated through qRT-PCR. Results We have found that: 1) system y+L activity is markedly lowered in monocytes and alveolar macrophages from the LPI patient, because of the prevailing expression of SLC7A7/y+LAT1 in these cells; 2) on the contrary, fibroblasts isolated from the same patient do not display the transport defect due to compensation by the SLC7A6/y+LAT2 isoform; 3) in both normal and LPI monocytes, GM-CSF induces the expression of SLC7A7, suggesting that the gene is a target of the cytokine; 4) GM-CSF-induced differentiation of LPI monocytes is comparable to that of normal cells, demonstrating that GM-CSF signalling is unaltered; 5) general and respiratory conditions of the patient, along with PAP-associated parameters, markedly improved after GM-CSF therapy through aerosolization. Conclusions Monocytes and macrophages, but not fibroblasts, derived from a LPI patient clearly display the defect in system y+L-mediated arginine transport. The different transport phenotypes are referable to the relative levels of expression of SLC7A7 and SLC7A6. Moreover, the expression of SLC7A7 is regulated by GM-CSF in monocytes, pointing to a role of y+LAT1 in the pathogenesis of LPI associated PAP.

Published
2010
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3. Successful whole lung lavage in pulmonary alveolar proteinosis secondary to lysinuric protein intolerance: a case report

Author

Baritussio Aldo, Bolongaro Antonia, Adami Andrea, Stella Giulia M, Rodi Giuseppe, Ceruti Michele, Pozzi Ernesto, and Luisetti Maurizio

Subjects
Medicine
Abstract

Abstract Background Pulmonary alveolar proteinosis (PAP) is a rare disease characterised by accumulation of lipoproteinaceous material within alveoli, occurring in three clinically distinct forms: congenital, acquired and secondary. Among the latter, lysinuric protein intolerance (LPI) is a rare genetic disorder caused by defective transport of cationic amino acids. Whole Lung Lavage (WLL) is currently the gold standard therapy for severe cases of PAP. Case presentation We describe the case of an Italian boy affected by LPI who, by the age of 10, developed digital clubbing and, by the age of 16, a mild restrictive functional impairment associated with a high-resolution computed tomography (HRCT) pattern consistent with pulmonary alveolar proteinosis. After careful assessment, he underwent WLL. Conclusion Two years after WLL, the patient has no clinical, radiological or functional evidence of pulmonary disease recurrence, thus suggesting that WLL may be helpful in the treatment of PAP secondary to LPI.

Published
2007
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5. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients

Author

Campo, Ilaria, primary, Carey, Brenna C., additional, Paracchini, Elena, additional, Kadija, Zamir, additional, De Silvestri, Annalisa, additional, Rodi, Giuseppe, additional, De Amici, Mara, additional, Torre, Cristina, additional, Zorzetto, Michele, additional, Griese, Matthias, additional, Meloni, Federica, additional, Corsico, Angelo Guido, additional, Trapnell, Bruce C., additional, and Mariani, Francesca, additional

Published
2023
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8. Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy

Author

Melazzini, Federica, Colaneri, Marta, Fumoso, Federica, Freddi, Giulia, Lenti, Marco Vincenzo, Pieri, Teresa Chiara, Piloni, Davide, Noris, Patrizia, Pieresca, Carla, Preti, Paola Stefania, Russo, Mariaconcetta, Corsico, Angelo, Tavazzi, Guido, Baldanti, Fausto, Triarico, Antonio, Mojoli, Francesco, Bruno, Raffaele, Di Sabatino, Antonio, Aronico, Nicola, Bergamaschi, Gaetano, Bertolino, Giampiera, Codega, Silvia, Costanzo, Filippo, Cresci, Roberto, Delliponti, Angela, Derosa, Giuseppe, Di Stefano, Michele, Falaschi, Francesco, Iadarola, Carmine, Lovati, Elisabetta, Lucotti, Pietro Carlo, Martignoni, Alessandra, Mengoli, Caterina, Miceli, Emanuela, Mugellini, Amedeo, Muggia, Chiara, Pagani, Elisabetta, Palumbo, Ilaria, Pecci, Alessandro, Perrone, Tiziano, Sgarlata, Carmelo, Siciliani, Luisa, Staniscia, Andrea, Vjera, Francesca Torello, Achilli, Giovanna, Agostinelli, Andrea, Antoci, Valentina, Ballesio, Alessia, Banfi, Francesco, Barteselli, Chiara, Benedetti, Irene, de Andreis, Federica Borrelli, Brattoli, Michele, Calabretta, Francesca, Cambiè, Ginevra, Canta, Roberta, Conca, Federico, Coppola, Luigi, Cremonte, Elisa Maria, Croce, Gabriele, Del Rio, Virginia, Di Terlizzi, Francesco, Ferrari, Maria Giovanna, Ferrari, Sara, Fiengo, Anna, Forni, Tommaso, Frigerio, Chiara, Fusco, Alessandra, Gabba, Margherita, Garolfi, Matteo, Gentile, Antonella, Gori, Giulia, Grandi, Giacomo, Grimaldi, Paolo, Lampugnani, Alice, Lapia, Francesco, Lepore, Federica, Lettieri, Gianluca, Mambella, Jacopo, Mercanti, Chiara, Merli, Stefania, Mordà, Francesco, Nardone, Alba, Pace, Luca, Padovini, Lucia, Parodi, Alessandro, Pellegrino, Ivan, Pitotti, Lavinia, Reduzzi, Margherita, Rigano, Giovanni, Romito, Giovanni, Rotola, Giorgio, Sabatini, Umberto, Salvi, Lucia, Santacroce, Giovanni, Savioli, Jessica, Soriano, Simone, Spataro, Carmine, Stefani, Debora, Aliberti, Anna Rita, Amatu, Alessandro, Anfossi, Laura, Arisi, Eric, Baldi, Chiara, Belliato, Mirko, Bellini, Lorenzo, Benzi, Alberto, Bichisao, Germana, Bolongaro, Antonia, Bottazzi, Andrea, Broglia, Federica, Bruschi, Giacomo, Caneva, Luca, Capaccio, Emanuele, Carboni, Valeria, Cavalloro, Fabrizio, Ciceri, Maria, Civardi, Luca, Delmonte, Maria Paola, Domenegati, Elisa Lucia, Ferrari, Federica, Ferrari, Fiorenza, Ferrari, Marta, Fuardo, Marinella, Gerletti, Maddalena Margherita, Gualdana, Simonetta, Ilardi, Marcella, Lo Coco, Claudia, Maggio, Giuseppe, Mascia, Maria Benedetta, Mencherini, Simonetta, Merati, Paola Maria, Mongodi, Silvia, Mori, Anna Maria, Morgante, Federica, Niebel, Thekla Larissa, Noli, Silvano, Orlando, Anita, Pagani, Michele, Passador, Debora, Pellicori, Simona, Perotti, Luciano, Picchioni, Raffaella, Poma, Silvia, Pozzi, Marco, Preti, Emanuela, Puce, Roberta, Radolovich, Danila Katia, Ragni, Gianluca, Repossi, Filippo, Riccardi, Francesca, Rizzardi, Roberto, Rodi, Giuseppe, Roldi, Emanuela, Rossi, Cristina, Sala Gallini, Giuseppe, Sciutti, Fabio, Sportiello, Debora, Ticozzelli, Giulia, Visconti, Federico, Zizzi, Silvia, Bagliani, Alessandro, Belotti, Corrado, Bossi, Chiara, Colombo, Andrea, Colombo, Costanza Natalia Julia, Cremascoli, Luca, Dammassa, Valentino, Discepoli, Roberto, Garlando, Maria Adelaide, Grandini, Filippo, Pellegrini, Andrea, Quaranta, Cecilia, Stella, Andrea, Torresani, Francesco, Mondelli, Mario, Brunetti, Enrico, Di Matteo, Angela, Seminari, Elena, Maiocchi, Laura, Zuccaro, Valentina, Pagnucco, Layla, Mariani, Bianca, Ludovisi, Serena, Lissandrin, Raffaella, Parisi, Aldo, Sacchi, Paolo, Patruno, Savino F. A., Michelone, Giuseppe, Gulminetti, Roberto, Zanaboni, Domenico, Novati, Stefano, Maserati, Renato, Orsolini, Paolo, Vecchia, Marco, Asperges, Erika, Di Filippo, Alessandro, Sambo, Margherita, Biscarini, Simona, Lupi, Matteo, Roda, Silvia, Gallazzi, Ilaria, Sachs, Michele, Valsecchi, Pietro, Ferrari, Alessandra, Bosio, Matteo, Cascina, Alessandro, Conio, Valentina, Di Domenica, Rita, Donnetta, Anna, Fraolini, Elia, Gualtieri, Giuseppe, Mangiarotti, Patrizia, Mariani, Francesca, Meloni, Federica, Oggionni, Tiberio, Pasturenzi, Lidia, Ronzoni, Vanessa, Saracino, Laura, Stella, Giulia, Tomaselli, Stefano, Abbate, Tommaso, Accordino, Giulia, Bertuccio, Francesco, Burattini, Cecilia, Cacciatore, Elisa, Cattaneo, Elena, Chino, Vittorio, Coretti, Manuela, Della Zoppa, Matteo, Infusino, Cristina, Lettieri, Sara, Maccabruni, Valeria, Mancinelli, Silvia, Tirelli, Claudio, and Vertui, Valentina

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), 030204 cardiovascular system & hematology, Single Center, Tertiary referral hospital, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Medicine, cardiovascular diseases, Mean platelet volume, biology, SARS-CoV-2, business.industry, Pulmonary embolism, C-reactive protein, Anticoagulants, Thrombosis, equipment and supplies, medicine.disease, Im - Original, 030220 oncology & carcinogenesis, biology.protein, Emergency Medicine, Observational study, business
Abstract

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score > 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p p p = 0.002 and p = 0.005, respectively). No significant difference was found in d-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

Published
2020
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11. Correction to: Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy

Author

Melazzini, Federica, Colaneri, Marta, Fumoso, Federica, Freddi, Giulia, Lenti, Marco Vincenzo, Pieri, Teresa Chiara, Piloni, Davide, Noris, Patrizia, Pieresca, Carla, Preti, Paola Stefania, Russo, Mariaconcetta, Corsico, Angelo, Tavazzi, Guido, Baldanti, Fausto, Triarico, Antonio, Mojoli, Francesco, Bruno, Raffaele, Di Sabatino, Antonio, Aronico, Nicola, Bergamaschi, Gaetano, Bertolino, Giampiera, Codega, Silvia, Costanzo, Filippo, Cresci, Roberto, Delliponti, Angela, Derosa, Giuseppe, Di Stefano, Michele, Falaschi, Francesco, Iadarola, Carmine, Lovati, Elisabetta, Lucotti, Pietro Carlo, Martignoni, Alessandra, Mengoli, Caterina, Miceli, Emanuela, Mugellini, Amedeo, Muggia, Chiara, Pagani, Elisabetta, Palumbo, Ilaria, Pecci, Alessandro, Perrone, Tiziano, Sgarlata, Carmelo, Siciliani, Luisa, Staniscia, Andrea, Vjera, Francesca Torello, Achilli, Giovanna, Agostinelli, Andrea, Antoci, Valentina, Ballesio, Alessia, Banfi, Francesco, Barteselli, Chiara, Benedetti, Irene, Borrelli de Andreis, Federica, Brattoli, Michele, Calabretta, Francesca, Cambiè, Ginevra, Canta, Roberta, Conca, Federico, Coppola, Luigi, Cremonte, Elisa Maria, Croce, Gabriele, Del Rio, Virginia, Di Terlizzi, Francesco, Ferrari, Maria Giovanna, Ferrari, Sara, Fiengo, Anna, Forni, Tommaso, Frigerio, Chiara, Fusco, Alessandra, Gabba, Margherita, Garolfi, Matteo, Gentile, Antonella, Gori, Giulia, Grandi, Giacomo, Grimaldi, Paolo, Lampugnani, Alice, Lapia, Francesco, Lepore, Federica, Lettieri, Gianluca, Mambella, Jacopo, Mercanti, Chiara, Merli, Stefania, Mordà, Francesco, Nardone, Alba, Pace, Luca, Padovini, Lucia, Parodi, Alessandro, Pellegrino, Ivan, Pitotti, Lavinia, Reduzzi, Margherita, Rigano, Giovanni, Romito, Giovanni, Rotola, Giorgio, Sabatini, Umberto, Salvi, Lucia, Santacroce, Giovanni, Savioli, Jessica, Soriano, Simone, Spataro, Carmine, Stefani, Debora, Aliberti, Anna Rita, Amatu, Alessandro, Anfossi, Laura, Arisi, Eric, Baldi, Chiara, Belliato, Mirko, Bellini, Lorenzo, Benzi, Alberto, Bichisao, Germana, Bolongaro, Antonia, Bottazzi, Andrea, Broglia, Federica, Bruschi, Giacomo, Caneva, Luca, Capaccio, Emanuele, Carboni, Valeria, Cavalloro, Fabrizio, Ciceri, Maria, Civardi, Luca, Delmonte, Maria Paola, Domenegati, Elisa Lucia, Ferrari, Federica, Ferrari, Fiorenza, Ferrari, Marta, Fuardo, Marinella, Gerletti, Maddalena Margherita, Gualdana, Simonetta, Ilardi, Marcella, Lo Coco, Claudia, Maggio, Giuseppe, Mascia, Maria Benedetta, Mencherini, Simonetta, Merati, Paola Maria, Mongodi, Silvia, Mori, Anna Maria, Morgante, Federica, Niebel, Thekla Larissa, Noli, Silvano, Orlando, Anita, Pagani, Michele, Passador, Debora, Pellicori, Simona, Perotti, Luciano, Picchioni, Raffaella, Poma, Silvia, Pozzi, Marco, Preti, Emanuela, Puce, Roberta, Radolovich, Danila Katia, Ragni, Gianluca, Repossi, Filippo, Riccardi, Francesca, Rizzardi, Roberto, Rodi, Giuseppe, Roldi, Emanuela, Rossi, Cristina, Sala Gallini, Giuseppe, Sciutti, Fabio, Sportiello, Debora, Ticozzelli, Giulia, Visconti, Federico, Zizzi, Silvia, Bagliani, Alessandro, Belotti, Corrado, Bossi, Chiara, Colombo, Andrea, Colombo, Costanza Natalia Julia, Cremascoli, Luca, Dammassa, Valentino, Discepoli, Roberto, Garlando, Maria Adelaide, Grandini, Filippo, Pellegrini, Andrea, Quaranta, Cecilia, Stella, Andrea, Torresani, Francesco, Mondelli, Mario, Brunetti, Enrico, Di Matteo, Angela, Seminari, Elena, Maiocchi, Laura, Zuccaro, Valentina, Pagnucco, Layla, Mariani, Bianca, Ludovisi, Serena, Lissandrin, Raffaella, Parisi, Aldo, Sacchi, Paolo, Patruno, Savino F. A., Michelone, Giuseppe, Gulminetti, Roberto, Zanaboni, Domenico, Novati, Stefano, Maserati, Renato, Orsolini, Paolo, Vecchia, Marco, Asperges, Erika, Di Filippo, Alessandro, Sambo, Margherita, Biscarini, Simona, Lupi, Matteo, Roda, Silvia, Gallazzi, Ilaria, Sachs, Michele, Valsecchi, Pietro, Ferrari, Alessandra, Bosio, Matteo, Cascina, Alessandro, Conio, Valentina, Di Domenica, Rita, Donnetta, Anna, Fraolini, Elia, Gualtieri, Giuseppe, Mangiarotti, Patrizia, Mariani, Francesca, Meloni, Federica, Oggionni, Tiberio, Pasturenzi, Lidia, Ronzoni, Vanessa, Saracino, Laura, Stella, Giulia, Tomaselli, Stefano, Abbate, Tommaso, Accordino, Giulia, Bertuccio, Francesco, Burattini, Cecilia, Cacciatore, Elisa, Cattaneo, Elena, Chino, Vittorio, Coretti, Manuela, Della Zoppa, Matteo, Infusino, Cristina, Lettieri, Sara, Maccabruni, Valeria, Mancinelli, Silvia, Tirelli, Claudio, and Vertui, Valentina

Subjects
Adult, Male, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), MEDLINE, Tertiary referral hospital, Single Center, Statistics, Nonparametric, Tertiary Care Centers, Prevalence, Internal Medicine, medicine, Humans, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Aged, Retrospective Studies, Aged, 80 and over, Academic Medical Centers, Task force, business.industry, Correction, COVID-19, Venous Thromboembolism, Middle Aged, Northern italy, Italy, Emergency medicine, Emergency Medicine, Female, business, Venous thromboembolism
Abstract

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown. On this basis, we conducted a retrospective, observational study on 259 consecutive COVID-19 patients admitted to an academic tertiary referral hospital in Northern Italy between March 19th and April 6th, 2020. Records of COVID-19 patients with a definite VTE event were reviewed for demographic information, co-morbidities, risk factors for VTE, laboratory tests, and anticoagulation treatment. Twenty-five cases among 259 COVID-19 patients developed VTE (9.6%), all of them having a Padua score 4, although being under standard anticoagulation prophylaxis since hospital admission. In the VTE subcohort, we found a significant positive correlation between platelet count (PLT) and either C reactive protein (CRP) (p 0.0001) or lactate dehydrogenase (LDH) (p = 0.0013), while a significant inverse correlation was observed between PLT and mean platelet volume (p 0.0001). Platelet-to-lymphocyte ratio significantly correlated with CRP (p 0.0001). The majority of VTE patients was male and younger compared to non-VTE patients (p = 0.002 and p = 0.005, respectively). No significant difference was found in D-dimer levels between VTE and non VTE patients, while significantly higher levels of LDH (p = 0.04) and IL-6 (p = 0.04) were observed in VTE patients in comparison to non-VTE patients. In conclusion, our findings showed a quite high prevalence of VTE in COVID-19 patients. Raised inflammatory indexes and increased serum levels of pro-inflammatory cytokines should raise the clinical suspicion of VTE.

Published
2021

12. Tidal Volume Reduction for Prevention of Ventilator-induced Lung Injury in Acute Respiratory Distress Syndrome

Author

BROCHARD, LAURENT, ROUDOT-THORAVAL, FRANÇOISE, ROUPIE, ERIC, DELCLAUX, CHRISTOPHE, CHASTRE, JEAN, FERNANDEZ-MONDÉJAR, ENRIQUE, CLÉMENTI, EVA, MANCEBO, JORDI, FACTOR, PHILLIP, MATAMIS, DIMITRI, RANIERI, MARCO, BLANCH, LLUIS, RODI, GIUSEPPE, MENTEC, HERVÉ, DREYFUSS, DIDIER, FERRER, MIGUEL, BRUN-BUISSON, CHRISTIAN, TOBIN, MARTIN, and LEMAIRE, FRANÇOIS

Published
1998
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13. The effectiveness of miniscrews in the three-dimensional control of a palatal impacted canine: “Canine Only” approach. Case report

Author

Annarumma, Fabio, D’Emidio, Martina, Rodi, Giuseppe, Battista, Gianni, Papi, Giulia, and Migliorati, Marco

Abstract

Treatment time and mechanics required to solve palatally impacted canines are usually challenging. Different biomechanics and protocol approaches are available, and among these, the use of skeletal anchorage as reactive unit can be noteworthy. The purpose of this article is to show a treatment of a palatally impacted canine by the means of a double miniscrew and cantilever system only. Two miniscrews with bracket heads were applied in a 16 years old patient; different cantilevers were used to solve the impaction and bring the canine in the right position. Results: the impacted canine was successfully moved into proper position with good three-dimensional control. Both miniscrews worked successfully as anchorage for the entire treatment. The palatally impacted canine was successfully treated utilizing two miniscrews and cantilever approach.

Published
2021
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14. A Global Survey on Whole Lung Lavage in Pulmonary Alveolar Proteinosis

Author

Arai, Toru, Bazhanov, Andrey A., Ben-Dov, Issahar, Bonella, Francesco, Braschi, Antonio, Casey, Alicia, Costabel, Ulrich, Cottin, Vincent, Dogru, Deniz, Gesierich, Wolfgang, Griese, Matthias, Grutters, Jan C., Halme, Maija, Henry, Michael, Herth, Felix J.F., Hui-ying, Wang, Ichiwata, Toshio, Ilkovich, Julia M., Inoue, Yoshikazu, Iotti, Giorgio A., Irani, Sarosh, Kolek, Vítězslav, Morais, António, Morgan, Cliff, Nicolai, Thomas, Novikova, Lubov N., Primhak, Robert, Reiter, Karl, Retsch-Bogart, George, Rodi, Giuseppe, Russi, Eric, Schmitz, Jochen, Schön, Carola, Schumann, Christian, Veltkamp, Marcel, Verwey, Charl, Wood, Robert E., Campo, Ilaria, Luisetti, Maurizio, Trapnell, Bruce C., Nakata, Koh, Van Moorsel, Coline H.M., Bonizzoni, Giacomo, and Tinelli, Carmine

Published
2016
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15. Additional file 1: of Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures

Author

Campo, Ilaria, Luisetti, Maurizio, Griese, Matthias, Trapnell, Bruce, Bonella, Francesco, Grutters, Jan, Koh Nakata, Moorsel, Coline Van, Costabel, Ulrich, Cottin, Vincent, Ichiwata, Toshio, Inoue, Yoshikazu, Braschi, Antonio, Bonizzoni, Giacomo, Iotti, Giorgio, Tinelli, Carmine, and Rodi, Giuseppe

Subjects
health care facilities, manpower, and services, education, respiratory system, health care economics and organizations
Abstract

Therapeutic lavage for pulmonary alveolar proteinosis. A questionnaire for an international survey. (DOCX 126 kb)

Published
2016
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16. Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures

Author

Campo, Ilaria, Luisetti, Maurizio, Griese, Matthias, Trapnell, Bruce C, Bonella, Francesco, Grutters, Jan, Nakata, Koh, Van Moorsel, Coline H M, Costabel, Ulrich, Cottin, Vincent, Ichiwata, Toshio, Inoue, Yoshikazu, Braschi, Antonio, Bonizzoni, Giacomo, Iotti, Giorgio A, Tinelli, Carmine, Rodi, Giuseppe, Arai, Toru, Bazhanov, AndreyA, Ben-Dov, Issahar, Casey, Alicia, Dogru, Deniz, Gesierich, Wolfgang, Grutters, JanC, Halme, Maija, Henry, Michael, Herth, FelixJ F, Hui-Ying, Wang, Ilkovich, JuliaM, Iotti, GiorgioA, Irani, Sarosh, Kolek, Vít?zslav, Morais, António, Morgan, Cliff, Nicolai, Thomas, Novikova, LubovN, Primhak, Robert, Reiter, Karl, Retsch-Bogart, George, Russi, Eric, Schmitz, Jochen, Schön, Carola, Schumann, Christian, Veltkamp, Marcel, Verwey, Charl, Wood, RobertE, Clinicum, Department of Medicine, and Keuhkosairauksien yksikkö

Subjects
Male, medicine.medical_specialty, Standard of care, Supine position, Medizin, Interstitial lung disease, Pulmonary Alveolar Proteinosis, Bronchoalveolar Lavage, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Whole lung lavage, Genetics(clinical), Pharmacology (medical), 030212 general & internal medicine, Lung, Genetics (clinical), Medicine(all), Left lung, business.industry, Research, General Medicine, medicine.disease, 3. Good health, Clinical Practice, medicine.anatomical_structure, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Emergency medicine, Female, Lung Diseases, Interstitial, Pulmonary alveolar proteinosis, business, Bronchoalveolar Lavage Fluid, Rare disease
Abstract

Background Whole lung lavage (WLL) is the current standard of care treatment for patients affected by pulmonary alveolar proteinosis (PAP). However, WLL is not standardized and international consensus documents are lacking. Our aim was to obtain a factual portrayal of WLL as currently practiced with respect to the procedure, indications for its use, evaluation of therapeutic benefit and complication rate. Methods A clinical practice survey was conducted globally by means of a questionnaire and included 27 centers performing WLL in pediatric and/or adult PAP patients. Results We collected completed questionnaires from 20 centres in 14 countries, practicing WLL in adults and 10 centers in 6 countries, practicing WLL in pediatric patients. WLL is almost universally performed under general anesthesia, with a double-lumen endobronchial tube in two consecutive sessions, with an interval of 1–2 weeks between sessions in approximately 50 % of centres. The use of saline warmed to 37 °C, drainage of lung lavage fluid by gravity and indications for WLL therapy in PAP were homogenous across centres. There was great variation in the choice of the first lung to be lavaged: 50 % of centres based the choice on imaging, whereas 50 % always started with the left lung. The choice of position was also widely discordant; the supine position was chosen by 50 % of centres. Other aspects varied significantly among centres including contraindications, methods and timing of follow up, use of chest percussion, timing of extubation following WLL and lung isolation and lavage methods for small children. The amount of fluid used to perform the WLL is a critical aspect. Whilst a general consensus exists on the single aliquot of fluid for lavage (around 800 ml of warm saline, in adults) great variability exists in the total volume instilled per lung, ranging from 5 to 40 liters, with an average of 15.4 liters/lung. Conclusions This international survey found that WLL is safe and effective as therapy for PAP. However these results also indicate that standardization of the procedure is required; the present survey represents the a first step toward building such a document. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0497-9) contains supplementary material, which is available to authorized users.

Published
2016

17. Additional file 2: of Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures

Author

Campo, Ilaria, Luisetti, Maurizio, Griese, Matthias, Trapnell, Bruce, Bonella, Francesco, Grutters, Jan, Koh Nakata, Moorsel, Coline Van, Costabel, Ulrich, Cottin, Vincent, Ichiwata, Toshio, Inoue, Yoshikazu, Braschi, Antonio, Bonizzoni, Giacomo, Iotti, Giorgio, Tinelli, Carmine, and Rodi, Giuseppe

Abstract

Pharmacologic approaches utilized to support WLL. (DOCX 14 kb)

Published
2016
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18. Inhaled sargramostim and whole lung lavage (WLL) as therapy of autoimmune pulmonary alveolar proteinosis (aPAP)

Author

Campo, Ilaria, primary, Mariani, Francesca, additional, Paracchini, Elena, additional, Kadija, Zamir, additional, Zorzetto, Michele, additional, Tinelli, Carmine, additional, Rodi, Giuseppe, additional, Meloni, Federica, additional, Griese, Matthias, additional, Trapnell, Bruce, additional, Scheuch, Gerhard, additional, Muellinger, Bernhard, additional, and Luisetti, Maurizio, additional

Published
2016
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19. A Global Survey on Whole Lung Lavage in Pulmonary Alveolar Proteinosis

Author

Campo, Ilaria, primary, Luisetti, Maurizio, additional, Griese, Matthias, additional, Trapnell, Bruce C., additional, Bonella, Francesco, additional, Grutters, Jan C., additional, Nakata, Koh, additional, Van Moorsel, Coline H.M., additional, Costabel, Ulrich, additional, Cottin, Vincent, additional, Ichiwata, Toshio, additional, Inoue, Yoshikazu, additional, Braschi, Antonio, additional, Bonizzoni, Giacomo, additional, Iotti, Giorgio A., additional, Tinelli, Carmine, additional, Rodi, Giuseppe, additional, Arai, Toru, additional, Bazhanov, Andrey A., additional, Ben-Dov, Issahar, additional, Casey, Alicia, additional, Dogru, Deniz, additional, Gesierich, Wolfgang, additional, Halme, Maija, additional, Henry, Michael, additional, Herth, Felix J.F., additional, Hui-ying, Wang, additional, Ilkovich, Julia M., additional, Irani, Sarosh, additional, Kolek, Vítězslav, additional, Morais, António, additional, Morgan, Cliff, additional, Nicolai, Thomas, additional, Novikova, Lubov N., additional, Primhak, Robert, additional, Reiter, Karl, additional, Retsch-Bogart, George, additional, Russi, Eric, additional, Schmitz, Jochen, additional, Schön, Carola, additional, Schumann, Christian, additional, Veltkamp, Marcel, additional, Verwey, Charl, additional, and Wood, Robert E., additional

Published
2016
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21. Assessment and management of pulmonary alveolar proteinosis in a reference center

Author

Campo, Ilaria, primary, Mariani, Francesca, additional, Rodi, Giuseppe, additional, Paracchini, Elena, additional, Tsana, Eric, additional, Piloni, Davide, additional, Nobili, Isabella, additional, Kadija, Zamir, additional, Corsico, Angelo, additional, Cerveri, Isa, additional, Chalk, Claudia, additional, Trapnell, Bruce C, additional, Braschi, Antonio, additional, Tinelli, Carmine, additional, and Luisetti, Maurizio, additional

Published
2013
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23. In Lysinuric Protein Intolerance system y+L activity is defective in monocytes and in GM-CSF-differentiated macrophages

Author

Barilli, Amelia, primary, Rotoli, Bianca Maria, additional, Visigalli, Rossana, additional, Bussolati, Ovidio, additional, Gazzola, Gian C, additional, Kadija, Zamir, additional, Rodi, Giuseppe, additional, Mariani, Francesca, additional, Ruzza, Maria Lorena, additional, Luisetti, Maurizio, additional, and Dall'Asta, Valeria, additional

Published
2010
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26. Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients.

Author

Campo I, Carey BC, Paracchini E, Kadija Z, De Silvestri A, Rodi G, De Amici M, Torre C, Zorzetto M, Griese M, Meloni F, Corsico AG, Trapnell BC, and Mariani F

Subjects
Humans, Granulocyte-Macrophage Colony-Stimulating Factor, Prospective Studies, Administration, Inhalation, Treatment Outcome, Bronchoalveolar Lavage, Oxygen therapeutic use, Surface-Active Agents therapeutic use, Biomarkers, Pulmonary Alveolar Proteinosis drug therapy, Pulmonary Alveolar Proteinosis pathology, Autoimmune Diseases drug therapy, Pulmonary Surfactants therapeutic use
Abstract

Rationale: Whole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP., Methods: 18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled "rescue" WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group., Results: The primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30 versus 18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar-arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported., Conclusions: This long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP., Competing Interests: Conflict of interest: I. Campo, B.C. Trapnell and B.C. Carey serve as investigators on another clinical trial of inhaled rGM-CSF therapy of autoimmune PAP. B.C. Trapnell and B.C. Carey have served as consultants regarding the development of inhaled rGM-CSF as therapy of aPAP. No other authors have no financial or other conflicts of interest to declare related to this work., (Copyright ©The authors 2024.)

Published
2024
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27. Whole lung lavage therapy for pulmonary alveolar proteinosis: a global survey of current practices and procedures.

Author

Campo I, Luisetti M, Griese M, Trapnell BC, Bonella F, Grutters J, Nakata K, Van Moorsel CH, Costabel U, Cottin V, Ichiwata T, Inoue Y, Braschi A, Bonizzoni G, Iotti GA, Tinelli C, and Rodi G

Subjects
Bronchoalveolar Lavage Fluid, Female, Humans, Lung metabolism, Lung pathology, Lung Diseases, Interstitial metabolism, Lung Diseases, Interstitial therapy, Male, Pulmonary Alveolar Proteinosis metabolism, Surveys and Questionnaires, Bronchoalveolar Lavage methods, Pulmonary Alveolar Proteinosis therapy
Abstract

Background: Whole lung lavage (WLL) is the current standard of care treatment for patients affected by pulmonary alveolar proteinosis (PAP). However, WLL is not standardized and international consensus documents are lacking. Our aim was to obtain a factual portrayal of WLL as currently practiced with respect to the procedure, indications for its use, evaluation of therapeutic benefit and complication rate., Methods: A clinical practice survey was conducted globally by means of a questionnaire and included 27 centers performing WLL in pediatric and/or adult PAP patients., Results: We collected completed questionnaires from 20 centres in 14 countries, practicing WLL in adults and 10 centers in 6 countries, practicing WLL in pediatric patients. WLL is almost universally performed under general anesthesia, with a double-lumen endobronchial tube in two consecutive sessions, with an interval of 1-2 weeks between sessions in approximately 50 % of centres. The use of saline warmed to 37 °C, drainage of lung lavage fluid by gravity and indications for WLL therapy in PAP were homogenous across centres. There was great variation in the choice of the first lung to be lavaged: 50 % of centres based the choice on imaging, whereas 50 % always started with the left lung. The choice of position was also widely discordant; the supine position was chosen by 50 % of centres. Other aspects varied significantly among centres including contraindications, methods and timing of follow up, use of chest percussion, timing of extubation following WLL and lung isolation and lavage methods for small children. The amount of fluid used to perform the WLL is a critical aspect. Whilst a general consensus exists on the single aliquot of fluid for lavage (around 800 ml of warm saline, in adults) great variability exists in the total volume instilled per lung, ranging from 5 to 40 liters, with an average of 15.4 liters/lung., Conclusions: This international survey found that WLL is safe and effective as therapy for PAP. However these results also indicate that standardization of the procedure is required; the present survey represents the a first step toward building such a document.

Published
2016
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