Evidence map›Paper›PMID 32897035›Full record

Trial reportThe New England journal of medicine2020

Inhaled Molgramostim Therapy in Autoimmune Pulmonary Alveolar Proteinosis.

Bruce C Trapnell, Yoshikazu Inoue, Francesco Bonella, Cliff Morgan, Stéphane Jouneau, Elisabeth Bendstrup, Ilaria Campo, Spyros A Papiris, Etsuro Yamaguchi, Erdogan Cetinkaya and 10 more

3 registry-linked trialsOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 55 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 5 pooled it
7.7field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00901511 phase2completednot on this map

Inhaled GM-CSF Reduces the Need for Whole Lung Lavage and Improves Gas Exchange in Autoimmune PAP Patients

TypeinterventionalSponsorFondazione IRCCS Policlinico San Matteo di PaviaRan2009 to 2016Enrolled18ConditionsAutoimmune Pulmonary Alveolar ProteinosisArmsBaseline WLL, Sargramostim, Rescue WLL
NCT02702180 phase2completednot on this map

A Randomised, Double-blind, Placebo-controlled Multicentre Clinical Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis Patients

TypeinterventionalSponsorSavara Inc.Ran2016 to 2019Enrolled139ConditionsAutoimmune Pulmonary Alveolar ProteinosisArmsMolgramostim, Placebo, PARI eFlow nebulizer system
NCT06546098 availablenot on this map

Expanded Access to Inhaled Molgramostim Nebulizer Solution in Adults With Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

Typeexpanded_accessSponsorSavara Inc.ConditionsAutoimmune Pulmonary Alveolar ProteinosisArmsMolgramostim nebulizer solution
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 5 syntheses or guidelines pooled it, 107 citations in OpenAlex.

  1. Pooled it
  2. The burden of autoimmune pulmonary alveolar proteinosis: a systematic review.European respiratory review : an official journal of the European Respiratory Society · 2026
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Trial
  8. Article
  9. Observational
  10. Article
  11. Article
  12. Outcomes and outcome measures in studies of pulmonary alveolar proteinosis: a scoping review.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 11 institutions in 13 countries.

Bruce C TrapnellFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Yoshikazu InoueFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).ORCID 0000-0003-3994-874X
Francesco BonellaFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Cliff MorganFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Stéphane JouneauFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Elisabeth BendstrupFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Ilaria CampoFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Spyros A PapirisFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Etsuro YamaguchiFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Erdogan CetinkayaFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Mikhail M IlkovichFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Mordechai R KramerFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Marcel VeltkampFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Michael KreuterFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Tomohisa BabaFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Cecilia GanslandtFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Inge TarnowFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Grant WatererFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
Taneli JouhikainenFrom the Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati (B.C.T.); National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka (Y.I.), Aichi Medical University Hospital, Nagakute, Aichi (E.Y.), and Kanagawa Cardiovascular and Respiratory Center, Yokohama (T.B.) - all in Japan; Outpatients Clinic for Interstitial and Rare Lung Disease, Ruhrlandklinik University Hospital, Essen (F.B.), and Center for Interstitial and Rare Lung Diseases, Pulmonology, Thoraxklinik, Heidelberg University Hospital, and German Center for Lung Research, Heidelberg (M.K.) - all in Germany; the Departments of Critical Care and Respiratory Medicine, Royal Brompton Hospital, London (C.M.); Respiratory Diseases Department, Pontchaillou Hospital, IRSET UMR 1085, Rennes 1 University, Rennes, France (S.J.); the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus (E.B.), and Savara, Horsholm (C.G., I.T.) - both in Denmark; the Pneumology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy (I.C.); the 2nd Pulmonary Medicine Department, General University Hospital "Attikon," Medical School, National and Kapodistrian University of Athens, Athens (S.A.P.); University of Health Sciences Turkey, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, Istanbul (E.C.); Pulmonary Clinic of St. Petersburg Pavlov State Medical University, St. Petersburg, Russia (M.M.I.); Institute of Pulmonary and Allergy Medicine, Rabin Medical Center, Petah Tikva, Israel (M.R.K.); ILD Center of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, the Netherlands (M.V.); the University of Western Australia, Royal Perth Hospital, Perth, Australia (G.W.); and Savara, Austin, TX (T.J.).
IMPALA Trial Investigators
Aichi Medical University Hospital · JPSavara (Denmark) · DKAarhus University Hospital · DKCincinnati Children's Hospital Medical Center · USFirst Pavlov State Medical University of St. Petersburg · RUHeidelberg University · DENational and Kapodistrian University of Athens · GRRabin Medical Center · ILRoyal Brompton Hospital · GBRuhrlandklinik · DEThe University of Western Australia · AU

Funding

Role of GM-CSF in Myeloid Cell Function and Innate ImmunityR01HL085453 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI TRAPNELL, BRUCE C · 2007 to 2023
$6.5M
RLDC: Molecular Pathway-Driven Diagnostics & Therapeutics for Rare Lung DiseasesU54HL127672 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI TRAPNELL, BRUCE C · 2014 to 2018
$3.7M
Role of S-nitrosothiols in Akt1 signaling and pneumonia resolutionK08HL130557 · NHLBI · DUKE UNIVERSITY · PI KRAFT, BRYAN D. · 2017 to 2021
$591k
NHLBI NIH HHS K08 HL130557NHLBI NIH HHS R01 HL085453NHLBI NIH HHS U54 HL127672
6 · The paper itself

Abstract

backgroundAutoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia. It is caused by disruption of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, which pulmonary alveolar macrophages require to clear surfactant. Recently, inhaled GM-CSF was shown to improve the partial pressure of arterial oxygen in patients with aPAP.

methodsIn a double-blind, placebo-controlled, three-group trial, we randomly assigned patients with aPAP to receive the recombinant GM-CSF molgramostim (300 μg once daily by inhalation), either continuously or intermittently (every other week), or matching placebo. The 24-week intervention period was followed by an open-label treatment-extension period. The primary end point was the change from baseline in the alveolar-arterial difference in oxygen concentration (A-aDo

resultsIn total, 138 patients underwent randomization; 46 were assigned to receive continuous molgramostim, 45 to receive intermittent molgramostim, and 47 to receive placebo. Invalid A-aDo

conclusionsIn patients with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. (Funded by Savara Pharmaceuticals; IMPALA ClinicalTrials.gov number, NCT02702180.).

Indexed as

Administration, InhalationAdultAutoimmune DiseasesBronchoalveolar LavageDouble-Blind MethodDrug Administration ScheduleExercise ToleranceFemaleGranulocyte-Macrophage Colony-Stimulating FactorHealth StatusHumansMaleMiddle AgedOxygenPulmonary Alveolar ProteinosisPulmonary Gas ExchangeGranulocyte-Macrophage Colony-Stimulating FactormolgramostimOxygenRecombinant Proteins

Identifiers

PMID32897035
PMCPMC8083051
OpenAlexW3083596123

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.