Advertisement

The Spectrum of Non-asthmatic Airway Diseases Contributing to Cough in the Adult

  • Sidney S. BramanEmail author
  • Armeen Poor
Chronic Cough (K Altman, Section Editor)
  • 1 Downloads
Part of the following topical collections:
  1. Topical Collection on Chronic Cough

Abstract

Purpose of Review

Cough becomes a pathologic reflex when the airways are inflamed and overwhelmed with excessive mucus. The goal of this review is to discuss acute and chronic cough syndromes caused by non-asthmatic airway diseases.

Recent Findings

Acute cough syndrome is short-lived and self-limited. Acute bronchitis and diffuse acute infectious bronchiolitis (DAIB) are examples. The former is usually caused by a viral illness; the latter by Mycoplasma pneumoniae, influenza, and Haemophilus influenzae. Causes of chronic cough in the adult include chronic bronchitis, non-infectious bronchiolitis, and non-cystic fibrosis bronchiectasis.

Summary

Supportive measures are recommended for acute bronchitis and antibiotic use is discouraged. Antibiotics may be needed for DAIB. Smoking cessation and bronchodilators can control cough in chronic bronchitis. Therapeutic approaches for non-infectious bronchiolitis depend on the varied etiology. The hallmark of bronchiectasis is a chronic infection of the airways, and antibiotics, mucus clearance measures, and bronchodilators are all supportive.

Keywords

Acute bronchitis Acute bronchiolitis Chronic cough Chronic bronchitis Non-infectious bronchiolitis Bronchiectasis 

Notes

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001–02. Vital Health Stat 13. 2006;159:1–66.Google Scholar
  2. 2.
    Cullinan P. Persistent cough and sputum: prevalence and clinical characteristics in Southeast England. Resp Med. 1992;86:143–9.Google Scholar
  3. 3.
    Chung KF, Pavrord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008;371:1364–74.Google Scholar
  4. 4.
    •• Irwin RS, French CL, Chang AB, Altman KW, on behalf of the CHEST Expert Cough Panel Classification of Cough as a Symptom in Adults and Management Algorithms. CHEST Guideline and Expert Panel Report. Chest. 2018;153(1):196–209. In 1966, the CHEST Expert Cough Panel classified cough as acute, subacute or chronic cough depending on the duration of the cough. This systematic review was an update that determined that this classification is useful in diagnosing and treating patients with cough around the globe. Previous algorithms were updated to reflect the advances in cough management as of 2017. Google Scholar
  5. 5.
    Morice A. Chronic cough: epidemiology. Chron Respir Dis. 2008;5(1):43–7.Google Scholar
  6. 6.
    Ford AC, Forman D, Moayyedi P, Morice AH. Cough in the community: a cross sectional survey and the relationship to gastrointestinal symptoms. Thorax. 2006;61:975–9.Google Scholar
  7. 7.
    Coultas DB, Mapel D, Gagnon R, Lydick E. The health impact of undiagnosed airflow obstruction in a national sample of United States adults. Am J Respir Crit Care Med. 2001;164(3):372–7.Google Scholar
  8. 8.
    •• Ma J, Rubin BK, Voynow JA. Mucins, mucus, and goblet cells. Chest. 2018;154(1):169–76. The major macromolecular components of mucus are the mucin glycoproteins which are critical for local defense of the airway. This review provides new data supporting the concept that not only are mucins and mucus important for lung homeostasis and protection from environmental threats, but also that goblet cells play an important role as regulators of innate immune function. The fact that mucins and goblet cells are important to innate immunity may shift the current paradigm of repressing increased mucin expression to a new approach of targeting regulation of specific mucins. Google Scholar
  9. 9.
    •• Miravitlles M, Kruesmann F, Haverstock D, Perroncel R, Choudhri SH, Arvis P. Sputum colour and bacteria in chronic bronchitis exacerbations: a pooled analysis. Eur Respir J. 2012;39(6):1354–60.  https://doi.org/10.1183/09031936.00042111. The correlation between sputum color and the presence of potentially pathogenic bacteria in acute exacerbations of COPD was studied. The authors found that green or yellow versus white sputum color was associated with a sensitivity of 94.7% and a specificity of 15% for the presence of bacteria. While sputum color was a stronger predictor of potentially pathogenic bacteria, it did not always predict the need for antibiotics. Google Scholar
  10. 10.
    • French CL, Irwin RS, Curley FJ, et al. Impact of chronic cough on quality of life. Arch Intern Med. 1998;158:1657–61. This study shows that chronic cough is associated with deterioration in patients' quality of life and that the health-related dysfunction was most likely psychosocial. Google Scholar
  11. 11.
    • Dicpinigaitis PV, Tso R, Banauch G. Prevalence of depressive symptoms among patients with chronic cough. Chest. 2006;130:1839–43. This study showed that depressive symptomatology is very common in patients with chronic cough. There was a statistically significant improvement in both cough and depression scores after 3 months of successful treatment. Google Scholar
  12. 12.
    National Hospital Ambulatory Medical Care Survey: 2011 outpatient department summary tables. http://www.cdc.gov/nchs/data/ahcd/nhamcs_ outpatient/2011_opd_web_tables.pdf. Accessed August 10th, 2018.
  13. 13.
    •• Kinkade S, Long NA. Acute bronchitis. Am Fam Physician. 2016;94(7):560–5. Cough is the most common illness-related reason for ambulatory care visits in the United States.When the cough is due to acute bronchitis it typically lasts about two to three weeks and is usually caused by viruses. This article offers a reminder that antibiotics are not indicated in patients without chronic lung disease. Radiography is warranted only when pneumonia is suspected. Google Scholar
  14. 14.
    Clark TW, Medina MJ, Batham S, Curran MD, Parmar S, Nicholson KG. Adults hospitalised with acute respiratory illness rarely have detectable bacteria in the absence of COPD or pneumonia; viral infection predominates in a large prospective UK sample. J Inf Secur. 2014;69(5):507–15.Google Scholar
  15. 15.
    van Vugt SF, Verheij TJ, de Jong PA, Butler CC, Hood K, Coenen S, et al. Diagnosing pneumonia in patients with acute cough: clinical judgment compared to chest radiography. Eur Respir J. 2013;42(4):1076–82.Google Scholar
  16. 16.
    Evertsen J, Baumgardner DJ, Regnery A, Banerjee I. Diagnosis and management of pneumonia and bronchitis in outpatient primary care practices. Prim Care Respir J. 2010;19(3):237–41.Google Scholar
  17. 17.
    •• Steurer J, Held U, Spaar A, et al. A decision aid to rule out pneumonia and reduce unnecessary prescriptions of antibiotics in primary care patients with cough and fever. BMC Med. 2011;9:56. These investigators offer a user-friendly decision aid to rule out pneumonia and thus reduce the rate of needless prescriptions of antibiotics. In patients with C-reactive protein values below 10 μg/ml or patients presenting with C-reactive protein between 11 and 50 μg/ml, but without dyspnoea and daily fever, pneumonia can be ruled out. By applying this rule in clinical practice they suggest that antibiotic prescription could be reduced by 9%. Google Scholar
  18. 18.
    Aabenhus R, Jensen JU, Jørgensen KJ, Hróbjartsson A, Bjerrum L. Bio-markers as point-of-care tests to guide prescription of antibiotics inpatients with acute respiratory infections in primary care. Cochrane Database Syst Rev. 2014;11:CD010130.Google Scholar
  19. 19.
    Schuetz P, Christ-crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–66.Google Scholar
  20. 20.
    Christ-crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006;174(1):84–93.Google Scholar
  21. 21.
    Christ-crain M, Jaccard-stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363(9409):600–7.Google Scholar
  22. 22.
    •• Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018;379(3):236–49. This study funded by funded by the National Institute of General Medical Sciences showed that the provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. Google Scholar
  23. 23.
    Braman SS. Chronic cough due to acute bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(1 Suppl):95S–103S.Google Scholar
  24. 24.
    •• Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;3:CD000245. This Cochrane Database Review concluded that there is limited evidence to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity the magnitude of this benefit needs to be considered in the broader context of potential side effects, cost and increased resistance to respiratory pathogens. Google Scholar
  25. 25.
    Hirschmann JV. Antibiotics for common respiratory tract infections in adults. Arch Intern Med. 2002;162(3):256–64.Google Scholar
  26. 26.
    Llor C, Moragas A, Bayona C, Morros R, Pera H, Plana-Ripoll O, et al. Efficacy of anti-inflammatory or antibiotic treatment in patients with non-complicated acute bronchitis and discoloured sputum: randomised placebo controlled trial. BMJ. 2013;347:f5762.Google Scholar
  27. 27.
    Becker LA, Hom J, Villasis-Keever M, van der Wouden JC. Beta2agonists for acute cough or a clinical diagnosis of acute bronchitis. Cochrane Database Syst Rev. 2015;9:CD001726.Google Scholar
  28. 28.
    Hay AD, Little P, Harnden A, et al. Effect of oral prednisolone on symptom duration and severity in nonasthmatic adults with acute lower respiratory tract infection: a randomized clinical trial. JAMA. 2017;318(8):721–30.Google Scholar
  29. 29.
    •• Kim V, Criner GJ. The chronic bronchitis phenotype in chronic obstructive pulmonary disease: features and implications. Curr Opin Pulm Med. 2015;21(2):133–41. Chronic bronchitis is associated with multiple clinical consequences, including hastening lung function decline, increasing risk of exacerbations, reducing health-related quality of life, and possibly raising all-cause mortality. While the main risk factor for chronic bronchitis is current smoking, exposure to air pollution, dusts and fumes and biomass fuels are newly described risk factors. This article reviews treatment options for COPD and chronic bronchitis including both pharmacologic and nonpharmacologic strategies. Google Scholar
  30. 30.
    Von Hertzen L, Reunanen A, Impivaara O, Mälkiä E, Aromaa A. Airway obstruction in relation to symptoms in chronic respiratory disease--a nationally representative population study. Respir Med. 2000;94(4):356–63.Google Scholar
  31. 31.
    Martinez CH, Kim V, Chen Y, Kazerooni EA, Murray S, Criner GJ, et al. The clinical impact of non-obstructive chronic bronchitis in current and former smokers. Respir Med. 2014;108(3):491–9.Google Scholar
  32. 32.
    Pelkonen MK, Notkola IL, Laatikainen TK, Koskela HO. Twenty-five year trends in prevalence of chronic bronchitis and the trends in relation to smoking. Respir Med. 2014;108(11):1633–40.Google Scholar
  33. 33.
    Pelkonen MK, Notkola IK, Laatikainen TK, Jousilahti P. Chronic bronchitis in relation to hospitalization and mortality over three decades. Respir Med. 2017;123:87–93.Google Scholar
  34. 34.
    •• Lahousse L, LJM S, Joos GF, Franco OH, Stricker BH, Brusselle GG. Epidemiology and impact of chronic bronchitis in chronic obstructive pulmonary disease. Eur Respir J. 2017;50(2). This study, the Rotterdam Study, investigated the impact of chronic bronchitis on the course of COPD including exacerbations and mortality risk in a prospective population-based cohort with long-term follow-up. It showed that COPD subjects with chronic bronchitis have an increased risk of exacerbations and respiratory mortality compared to COPD subjects without chronic phlegm production. Google Scholar
  35. 35.
    Kim V, Criner GJ. Chronic bronchitis and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013;187(3):228–37.Google Scholar
  36. 36.
    Kesimer M, Ford AA, Ceppe A, et al. Airway mucin concentration as a marker of chronic bronchitis. N Engl J Med. 2017;377(10):911–22.Google Scholar
  37. 37.
    Kim V, Oros M, Durra H, Kelsen S, Aksoy M, Cornwell WD, et al. Chronic bronchitis and current smoking are associated with more goblet cells in moderate to severe COPD and smokers without airflow obstruction. PLoS One. 2015;10(2):e0116108.Google Scholar
  38. 38.
    Viegi G, Paoletti P, Prediletto R, Carrozzi L, Fazzi P, di Pede F, et al. Prevalence of respiratory symptoms in an unpolluted area of northern Italy. Eur Respir J. 1988;1:311–8.Google Scholar
  39. 39.
    Cerveri I, Accordini S, Verlato G, Corsico A, Zoia MC, Casali L, et al. Variations in the prevalence across countries of chronic bronchitis and smoking habits in young adults. Eur Respir J. 2001;18(1):85–92.Google Scholar
  40. 40.
    Pelkonen M, Notkola IL, Nissinen A, Tukiainen H, Koskela H. Thirty-year cumulative incidence of chronic bronchitis and COPD in relation to 30-year pulmonary function and 40-year mortality: a follow-up in middle-aged rural men. Chest. 2006;130(4):1129–37.Google Scholar
  41. 41.
    •• Kim V, Zhao H, Boriek AM, et al. Persistent and newly developed chronic bronchitis are associated with worse outcomes in chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2016;13(7):1016–25. This Genetic Epidemiology of COPD (COPDGene) Study ascertained the relationship between smoking status and the presence or absence of chronic bronchitis and the subsequent effects on symptoms and outcomes. The study concluded that persistent and newly developed chronic bronchitis are associated with continued or resumed smoking, greater respiratory symptoms, worse health-related quality of life, worse lung function, and greater exacerbation frequency. These findings stress the importance of repeatedly assessing chronic cough and sputum production in smokers to identify those at risk for poor outcomes. Google Scholar
  42. 42.
    Ghafouri MA, Patil KD, Kass I. Sputum changes associated with the use of ipratropium bromide. Chest. 1984;86(3):387–93.Google Scholar
  43. 43.
    Casaburi R, Briggs DD, Donohue JF, Serby CW, Menjoge SS, Witek TJ. The spirometric efficacy of once-daily dosing with tiotropium in stable COPD: a 13-week multicenter trial. The US Tiotropium Study Group. Chest. 2000;118(5):1294–302.Google Scholar
  44. 44.
    Shapiro et al. Salmeterol combined with fluticasone reduces exacerbations more effectively in chronic bronchitis associated with chronic obstructive pulmonary disease: a post-hoc analysis of the TORCH Trial, American Thoracic Society Conference, B33 COPD, 2018.Google Scholar
  45. 45.
    •• Cazzola M, Calzetta L, Page C, et al. Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis. Eur Respir Rev. 2015;24(137):451–61. This meta-analysis determined the possible role of Nacetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD). They found a substantial difference between the responses induced by low (≤ 600 mg per day) and high (> 600 mg per day) doses of NAC. They concluded that NAC should be administered at a dose of ≥ 1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient. Google Scholar
  46. 46.
    •• Martinez FJ, Rabe KF, Sethi S, et al. Effect of roflumilast and inhaled corticosteroid/long-acting β2-agonist on chronic obstructive pulmonary disease exacerbations (RE(2)SPOND). A randomized clinical trial. Am J Respir Crit Care Med. 2016;194(5):559–67. This group studied COPD patients who at risk for exacerbations to determine whether roflumilast reduces moderate and/or severe chronic obstructive pulmonary disease exacerbations despite treatment with inhaled corticosteroid/long-acting β2-agonist with or without a longacting muscarinic antagonist (LAMA). Roflumilast did improve lung function and reduced exacerbations in participants with frequent exacerbations and/or hospitalization history. As expected because of the known gastrointestinal side effects of Roflumilast,adverse event-related discontinuations occurred in 11.7% roflumilast-treated and 5.4% placebo-treated participants. Google Scholar
  47. 47.
    Colby TV. Bronchiolitis. Pathologic considerations. Am J Clin Pathol. 1998;109(1):101–9.Google Scholar
  48. 48.
    Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med. 2003;168(11):1277–92.Google Scholar
  49. 49.
    •• Garibaldi BT, Illei P, Danoff SK. Bronchiolitis. Immunol Allergy Clin North Am. 2012;32(4):601–19. This review discusses several causes of bronchiolitis including infection, toxic exposure, collagen vascular disease, post lung and stem cell transplant, and idiopathic etiology. Radiographic features are presented with examples of air trapping with mosaic attenuation, thickened bronchial walls, and the presence of centrilobular nodules. Google Scholar
  50. 50.
    Devakonda A, Raoof S, Sung A, Travis WD, Naidich D. Bronchiolar disorders: a clinical-radiological diagnostic algorithm. Chest. 2010;137(4):938–51.Google Scholar
  51. 51.
    •• Ryu K, Takayanagi N, Ishiguro T, et al. Etiology and outcome of diffuse acute infectious bronchiolitis in adults. Ann Am Thorac Soc. 2015;12(12):1781–7. This group investigated diffuse acute infectious bronchiolitis (DAIB) in adults, a diagnosis confirmed in patients with acute feverish lower respiratory tract infection and chest computed tomography demonstrating mainly multiple centrilobular nodules in four or more lobes. The etiology was determined in 80%. Detected organisms included Mycoplasma pneumoniae, influenza virus, influenza virus with Streptococcus pneumoniae, Haemophilus influenzae, respiratory syncytial virus and rhinovirus. None of the patients with DAIB developed postinfectious bronchiolitis obliterans. Google Scholar
  52. 52.
    Tashtoush B, Okafor NC, Ramirez JF, Smolley L. Follicular bronchiolitis: a literature review. J Clin Diagn Res. 2015;9(9):OE01–5.Google Scholar
  53. 53.
    Niewoehner DE, Kleinerman J, Rice DB. Pathologic changes in the peripheral airways of young cigarette smokers. N Engl J Med. 1974;291(15):755–8.Google Scholar
  54. 54.
    •• Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. N Engl J Med. 2014;370(19):1820–8. This review focused on: 1)the recognition of obliterative bronchiolitis as an occupational disease, 2) the frequent occurrence of the bronchiolitis obliterans syndrome after allogeneic hematopoietic stem-cell transplantation (HSCT) or lung transplantation, and 3) the difficulties in establishing the diagnosis, 4) current therapeutic options. Google Scholar
  55. 55.
    Perez T, Remy-jardin M, Cortet B. Airways involvement in rheumatoid arthritis: clinical, functional, and HRCT findings. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1658–65.Google Scholar
  56. 56.
    Christie JD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Dobbels F, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant. 2012;31(10):1073–86.Google Scholar
  57. 57.
    Williams KM, Cheng GS, Pusic I, Jagasia M, Burns L, Ho VT, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(4):710–6.Google Scholar
  58. 58.
    Kingah PL, Muma G, Soubani A. Azithromycin improves lung function in patients with post-lung transplant bronchiolitis obliterans syndrome: a meta-analysis. Clin Transpl. 2014;28(8):906–10.Google Scholar
  59. 59.
    Safavi S, Prayle AP, Hall IP, Parmar J. Azithromycin for treatment of bronchiolitis obliterans syndrome in adult lung transplant recipients. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD012782.Google Scholar
  60. 60.
    Ruttens D, Verleden SE, Demeyer H, van Raemdonck DE, Yserbyt J, Dupont LJ, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a randomized controlled trial. PLoS One. 2018;13(4):e0193564.Google Scholar
  61. 61.
    •• McShane PJ, Tino G. Bronchiectasis. Chest. 2018 Nov 4. [Epub ahead of print] Review. This review is an update on the epidemiology, current diagnostic methods and treatment of bronchiectasis. It reports on three successful trials demonstrating that macrolides reduce exacerbations in bronchiectasis and a robust study on airway clearance therapy. It offers clinical tools that have been developed to quantify disease severity and predict prognosis. Google Scholar
  62. 62.
    Chotirmall SH. One small step for neutrophils, one giant leap for bronchiectasis. Am J Respir Crit Care Med. 2018;198(7):828–30.Google Scholar
  63. 63.
    Bedi P, Davidson DJ, McHugh BJ, Rossi AG, Hill AT. Blood neutrophils are reprogrammed in bronchiectasis. Am J Respir Crit Care Med. 2018;198:880–90.Google Scholar
  64. 64.
    •• Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J. 2015;45(5):1446–62. This article discussee the goals of therapy for bronchiectasis: to improve airway mucus clearance; to suppress, eradicate and prevent airway bacterial colonization; to reduce airway inflammation; and to improve physical functioning and quality of life. It reports on an increasing body of evidence on recent randomized controlled trials that support interventions in bronchiectasis. Google Scholar
  65. 65.
    Tsang KW, Tan KC, Ho PL, Ooi GC, Ho JC, Mak J, et al. Inhaled fluticasone in bronchiectasis: a 12 month study. Thorax. 2005;60:239–43.Google Scholar
  66. 66.
    Kapur N, Bell S, Kolbe J, et al. Inhaled steroids for bronchiectasis. Cochrane Database Syst Rev. 2009;1:CD000996.Google Scholar
  67. 67.
    Andréjak C, Nielsen R, Thomsen VØ, Duhaut P, Sørensen HT, Thomsen RW. Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis. Thorax. 2013;68(3):256–62.Google Scholar
  68. 68.
    Tsang KW, Ho PI, Chan KN, et al. A pilot study of low-dose erythromycin in bronchiectasis. Eur Respir J. 1999;13:361–4.Google Scholar
  69. 69.
    Cymbala AA, Edmonds AC, Bauer MA, et al. The disease modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis. Treat Respir Med. 2005;4:117–22.Google Scholar
  70. 70.
    •• Chalmers JD, Restrepo MI. Bronchiectasis management: the state of the union. Chest. 2017;152(6):1097–9. This is an editorial that discusses a companion article (Henkle et al Chest 2017;152:1120-1127 on the patterns of pharmacotherapy in patients with a diagnosis of bronchiectasis across the United States. It suggests that this work is starting point for where we need to go now with bronchiectasis research. Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Icahn School of Medicine at Mount SinaiNew YorkUSA
  2. 2.Pulmonary and Critical Care MedicineIcahn School of Medicine at Mount SinaiNew YorkUSA

Personalised recommendations