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Current HIV/AIDS Reports

, Volume 16, Issue 4, pp 359–369 | Cite as

Obstructive Lung Disease in HIV—Phenotypes and Pathogenesis

  • Deepti SinghviEmail author
  • Jessica Bon
  • Alison Morris
HIV Pathogenesis and Treatment (AL Landay and NS Utay, Section Editors)
Part of the following topical collections:
  1. Topical Collection on HIV Pathogenesis and Treatment

Abstract

Purpose of Review

In the antiretroviral therapy era, people living with HIV (PLWH) are surviving to older ages. Chronic illnesses such as chronic obstructive pulmonary disease (COPD) occur more frequently. COPD is often described as a single entity, yet multiple manifestations may be considered phenotypes. HIV is an independent risk factor for certain COPD phenotypes, and mechanisms underlying pathogenesis of these phenotypes may differ and impact response to therapy.

Recent Findings

Impaired diffusing capacity, airflow obstruction, and radiographic emphysema occur in PLWH and are associated with increased mortality. Age, sex, tobacco, and HIV-specific factors likely modulate the severity of disease. An altered lung microbiome and residual HIV in the lung may also influence phenotypes.

Summary

COPD is prevalent in PLWH with multiple phenotypes contributing to the burden of disease. HIV-specific factors and the respiratory microbiome influence disease pathogenesis. As tobacco use remains a significant risk factor for COPD, smoking cessation must be emphasized for all PLWH.

Keywords

Chronic obstructive HIV Pulmonary Emphysema Phenotypes Pathogenesis 

Notes

Compliance with Ethical Standards

Conflict of Interest

Deepti Singhvi declares that she has no conflict of interest.

Jessica Bon declares that she has received grants from the NIH and the VA.

Alison Morris has received grants from the NIH and Gilead.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

References

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

  1. 1.
    Global HIV & AIDS statistics — 2018 fact sheet | UNAIDS. http://www.unaids.org/en/resources/fact-sheet. Accessed 23 Feb 2019.
  2. 2.
    Maitre T, Cottenet J, Beltramo G, Georges M, Blot M, Piroth L, et al. Increasing burden of noninfectious lung disease in persons living with HIV: a 7-year study using the French nationwide hospital administrative database. Eur Respir J. 2018;52:1800359.  https://doi.org/10.1183/13993003.00359-2018.CrossRefPubMedGoogle Scholar
  3. 3.
    • Bigna JJ, Kenne AM, Asangbeh SL, Sibetcheu AT. Prevalence of chronic obstructive pulmonary disease in the global population with HIV: a systematic review and meta-analysis. Lancet Glob Health. 2018;6:e193–202. This study established the global prevalence of COPD in PLWH to be 10.6%, with a persistent association between COPD and HIV even when controlling for tobacco use. A higher prevalence was seen in those with higher income, more tobacco use, detectable viral load, and from European countries. CrossRefPubMedGoogle Scholar
  4. 4.
    Crothers K, Butt AA, Gibert CL, Rodriguez-Barradas MC, Crystal S, Justice AC, et al. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006;130:1326–33.CrossRefPubMedGoogle Scholar
  5. 5.
    Crothers K, Huang L, Goulet JL, Goetz MB, Brown ST, Rodriguez-Barradas MC, et al. HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era. Am J Respir Crit Care Med. 2011;183:388–95.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Drummond MB, Merlo CA, Astemborski J, Kalmin MM, Kisalu A, Mcdyer JF, et al. The effect of HIV infection on longitudinal lung function decline among IDUs: a prospective cohort. AIDS. 2013;27:1303–11.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Drummond MB, Kunisaki KM, Huang L. Obstructive lung diseases in HIV: a clinical review and identification of key future research needs. Semin Respir Crit Care Med. 2016;37:277–88.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Makinson A, Hayot M, Eymard-Duvernay S, Ribet C, Raffi F, Pialoux G, et al. HIV is associated with airway obstruction: a matched controlled study. AIDS. 2018;32:227–32.PubMedGoogle Scholar
  9. 9.
    Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: 2019 report. http://www.goldcopd.org. Accessed 22 Feb 2019.
  10. 10.
    Han MK, Agusti A, Calverley PM, et al. Chronic obstructive pulmonary disease phenotypes: the future of COPD. Am J Respir Crit Care Med. 2010;182:598–604.CrossRefPubMedGoogle Scholar
  11. 11.
    Sampériz G, Guerrero D, López M, Valera JL, Iglesias A, Ríos Á, et al. Prevalence of and risk factors for pulmonary abnormalities in HIV-infected patients treated with antiretroviral therapy. HIV Med. 2014;15:321–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Gingo MR, George MP, Kessinger CJ, Lucht L, Rissler B, Weinman R, et al. Pulmonary function abnormalities in HIV-infected patients during the current antiretroviral therapy era. Am J Respir Crit Care Med. 2010;182:790–6.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    George MP, Kannass M, Huang L, Sciurba FC, Morris A. Respiratory symptoms and airway obstruction in HIV-infected subjects in the HAART era. PLoS One. 2009;4:e6328.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ronit A, Lundgren J, Afzal S, Benfield T, Roen A, Mocroft A, et al. Airflow limitation in people living with HIV and matched uninfected controls. Thorax. 2018;73:431–8.CrossRefPubMedGoogle Scholar
  15. 15.
    • Risso K, Guillouet-de-Salvador F, Valerio L, Puglièse P, Naqvi A, Durant J, et al. COPD in HIV-infected patients: CD4 cell count highly correlated. PLoS One. 2017;12:e0169359. This study, a single center cross-sectional analysis of HIV-infected patients in France, found that low CD4 cell count and a low nadir CD4 cell count are independently associated with a diagnosis of COPD. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hirani A, Cavallazzi R, Vasu T, Pachinburavan M, Kraft WK, Leiby B, et al. Prevalence of obstructive lung disease in HIV population: a cross sectional study. Respir Med. 2011;105:1655–61.CrossRefPubMedGoogle Scholar
  17. 17.
    •• Li Y, Nouraie SM, Kessinger C, Weinman R, Huang L, Greenblatt RM, et al. Factors associated with progression of lung function abnormalities in HIV-infected individuals. J Acquir Immune Defic Syndr. 2018;79:501–9. This study demonstrated decreased DLCO in 79% of PLWH with faster rates of FEV1 decline in patients who were male with higher GOLD stage and older age. There was no difference in baseline FEV1 based on CD4 + count, viral load, or ART use. CrossRefPubMedGoogle Scholar
  18. 18.
    Drummond MB, Kirk GD, Astemborski J, McCormack MC, Marshall MM, Mehta SH, et al. Prevalence and risk factors for unrecognized obstructive lung disease among urban drug users. Int J Chron Obstruct Pulmon Dis. 2011;6:89–95.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Vestbo J, Edwards LD, Scanlon PD, Yates JC, Agusti A, Bakke P, et al. Changes in forced expiratory volume in 1 second over time in COPD. N Engl J Med. 2011;365:1184–92.CrossRefPubMedGoogle Scholar
  20. 20.
    Casanova C, de Torres JP, Aguirre-Jaíme A, Pinto-Plata V, Marin JM, Cordoba E, et al. The progression of chronic obstructive pulmonary disease is heterogeneous: the experience of the BODE cohort. Am J Respir Crit Care Med. 2011;184:1015–21.CrossRefPubMedGoogle Scholar
  21. 21.
    • MacDonald DM, Melzer AC, Collins G, et al. Smoking and accelerated lung function decline in HIV-positive individuals: a secondary analysis of the START pulmonary substudy. J Acquir Immune Defic Syndr. 2018;79:e85–92. In this secondary analysis of the START pulmonary substudy, the authors found a faster rate of annual decline in FEV1 in HIV-infected smokers compared to nonsmokers. CrossRefGoogle Scholar
  22. 22.
    •• Kunisaki KM, Niewoehner DE, Collins G, Aagaard B, Atako NB, Bakowska E, et al. Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial. Lancet Respir Med. 2016;4:980–9. This was a pulmonary substudy of a randomized controlled trial in which participants with HIV infection were randomized to immediate initiation of ART versus deferred until CD4 + cell count < 350 cells/μl. No difference was found between these groups in the rate of annual FEV1 decline, suggesting that the use of ART does not impact lung function decline. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Crothers K, McGinnis K, Kleerup E, Wongtrakool C, Hoo GS, Kim J, et al. HIV infection is associated with reduced pulmonary diffusing capacity. J Acquir Immune Defic Syndr. 2013;64:271–8.CrossRefPubMedGoogle Scholar
  24. 24.
    Fitzpatrick ME, Gingo MR, Kessinger C, Lucht L, Kleerup E, Greenblatt RM, et al. HIV infection is associated with diffusing capacity impairment in women. J Acquir Immune Defic Syndr. 2013;64:284–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Gingo MR, He J, Wittman C, Fuhrman C, Leader JK, Kessinger C, et al. Contributors to diffusion impairment in HIV-infected persons. Eur Respir J. 2014;43:195–203.CrossRefPubMedGoogle Scholar
  26. 26.
    Neas LM, Schwartz J. The determinants of pulmonary diffusing capacity in a national sample of U.S. adults. Am J Respir Crit Care Med. 1996;153:656–64.CrossRefPubMedGoogle Scholar
  27. 27.
    Morris A, Fitzpatrick M, Bertolet M, Qin S, Kingsley L, Leo N, et al. Use of rosuvastatin in HIV-associated chronic obstructive pulmonary disease. AIDS. 2017;31:539–44.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Diaz PT, King MA, Pacht ER, Wewers MD, Gadek JE, Nagaraja HN, et al. Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med. 2000;132:369–72.CrossRefGoogle Scholar
  29. 29.
    Attia EF, Akgün KM, Wongtrakool C, Goetz MB, Rodriguez-Barradas MC, Rimland D, et al. Increased risk of radiographic emphysema in HIV is associated with elevated soluble CD14 and nadir CD4. Chest. 2014;146:1543–53.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Leader JK, Crothers K, Huang L, King MA, Morris A, Thompson BW, et al. Risk factors associated with quantitative evidence of lung emphysema and fibrosis in an HIV-infected cohort. J Acquir Immune Defic Syndr. 2016;71:420–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    •• Triplette M, Attia EF, Akgün KM, Soo Hoo GW, Freiberg MS, Butt AA, et al. A low peripheral blood CD4/CD8 ratio is associated with pulmonary emphysema in HIV. PLoS One. 2017;12:e0170857. In this study, the authors found that a low peripheral CD4:CD8 ratio is associated with radiographic emphysema and low DLCO in PLWH, suggesting that this blood test may be able to be used as a marker of emphysema in PLWH. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    •• Leung JM, Malagoli A, Santoro A, Besutti G, Ligabue G, Scaglioni R, et al. Emphysema distribution and diffusion capacity predict emphysema progression in human immunodeficiency virus infection. PLoS One. 2016;11:e0167247. This study demonstrated that emphysema progression can be predicted based on radiographic emphysema distribution and DLCO values. PLWH who were more likely to have emphysema progression had higher baseline emphysema score and greater smoking exposure history. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Guaraldi G, Besutti G, Scaglioni R, Santoro A, Zona S, Guido L, et al. The burden of image based emphysema and bronchiolitis in HIV-infected individuals on antiretroviral therapy. PLoS One. 2014;9:e109027.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mannino DM, Thorn D, Swensen A, Holguin F. Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD. Eur Respir J. 2008;32:962–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Bon J, Fuhrman CR, Weissfeld JL, Duncan SR, Branch RA, Chang CCH, et al. Radiographic emphysema predicts low bone mineral density in a tobacco-exposed cohort. Am J Respir Crit Care Med. 2011;183:885–90.CrossRefPubMedGoogle Scholar
  36. 36.
    Hegerl U, Mergl R. Depression and suicidality in COPD: understandable reaction or independent disorders? Eur Respir J. 2014;44:734–43.CrossRefPubMedGoogle Scholar
  37. 37.
    Bloch M. Frailty in people living with HIV. AIDS Res Ther. 2018;15:19.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Kooij KW, Wit FWNM, Schouten J, van der Valk M, Godfried MH, Stolte IG, et al. HIV infection is independently associated with frailty in middle-aged HIV type 1-infected individuals compared with similar but uninfected controls. AIDS. 2016;30:241–50.CrossRefPubMedGoogle Scholar
  39. 39.
    • Akgün KM, Tate JP, Oursler KK, Crystal S, Leaf DA, Womack JA, et al. Association of chronic obstructive pulmonary disease with frailty measurements in HIV-infected and uninfected veterans. AIDS. 2016;30:2185–93. This study identified that while COPD is strongly associated with frailty in both HIV-infected and HIV-uninfected individuals, there is a stronger association in HIV-infected individuals. COPD is an independent risk factor for frailty in PLWH. CrossRefPubMedGoogle Scholar
  40. 40.
    Sin DD, Man JP, Man SFP. The risk of osteoporosis in Caucasian men and women with obstructive airways disease. Am J Med. 2003;114:10–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Bonjoch A, Figueras M, Estany C, Perez-Alvarez N, Rosales J, del Rio L, et al. High prevalence of and progression to low bone mineral density in HIV-infected patients: a longitudinal cohort study. AIDS. 2010;24:2827–33.CrossRefPubMedGoogle Scholar
  42. 42.
    Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011;53:1120–6.CrossRefPubMedGoogle Scholar
  43. 43.
    • Petraglia A, Leader JK, Gingo M, Fitzpatrick M, Ries J, Kessinger C, et al. Emphysema is associated with thoracic vertebral bone attenuation on chest CT scan in HIV-infected individuals. PLoS One. 2017;12:e0176719. The authors in this study measured thoracic vertebral bone attenuation as a surrogate for bone mineral density on CT chest imaging in PLWH. They found that greater emphysema is independently associated with lower bone mineral density in PLWH and the use of ART further reduces this bone mineral density. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M, et al. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. 2011;53:1130–9.CrossRefPubMedGoogle Scholar
  45. 45.
    Alwan A. (2011). Burden: mortality, morbidity, and risk factors. Global status report on noncommunicable diseases (pp. 9-31). Geneva, Switzerland: World Health Organization.Google Scholar
  46. 46.
    Chandra D, Gupta A, Leader JK, Fitzpatrick M, Kingsley LA, Kleerup E, et al. Assessment of coronary artery calcium by chest CT compared with EKG-gated cardiac CT in the multicenter AIDS cohort study. PLoS One. 2017;12:e0176557.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    • Besutti G, Raggi P, Zona S, Scaglioni R, Santoro A, Orlando G, et al. Independent association of subclinical coronary artery disease and emphysema in HIV-infected patients. HIV Med. 2016;17:178–87. This study scored emphysema and coronary artery calcium on CT chest radiographs from PLWH and found the presence of emphysema is independently associated with a positive coronary artery calcium score. Radiographic emphysema was also associated with a CD4 + count nadir < 200 cells/μl. CrossRefPubMedGoogle Scholar
  48. 48.
    Morris A, Gingo MR, George MP, Lucht L, Kessinger C, Singh V, et al. Cardiopulmonary function in individuals with HIV infection in the antiretroviral therapy era. AIDS. 2012;26:731–40.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Brittain EL, Duncan MS, Chang J, Patterson OV, DuVall SL, Brandt CA, et al. Increased echocardiographic pulmonary pressure in HIV-infected and -uninfected individuals in the veterans aging cohort study. Am J Respir Crit Care Med. 2018;197:923–32.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    •• Triplette M, Justice A, Attia EF, Tate J, Brown ST, Goetz MB, et al. Markers of chronic obstructive pulmonary disease are associated with mortality in people living with HIV. AIDS. 2018;32:487–93. This study demonstrated that airflow obstruction, DLCO, and emphysema are associated with increased mortality, independent of smoking exposure, in PLWH. PubMedPubMedCentralGoogle Scholar
  51. 51.
    •• Gingo MR, Nouraie M, Kessinger CJ, Greenblatt RM, Huang L, Kleerup EC, et al. Decreased lung function and all-cause mortality in HIV-infected individuals. Ann Am Thorac Soc. 2018;15:192–9. This study reported that both obstruction (FEV1/FVC < 0.7) and diffusion impairment (DLCO<60%) are associated with increased mortality in PLWH. The decrease in the Kaplan-Meier curve occurs earlier in time for diffusion impairment, suggesting that this may be an earlier marker of mortality. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Shirley DK, Kaner RJ, Glesby MJ. Effects of smoking on non-AIDS-related morbidity in HIV-infected patients. Clin Infect Dis. 2013;57:275–82.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Popescu I, Drummond MB, Gama L, Coon T, Merlo CA, Wise RA, et al. Activation-induced cell death drives profound lung CD4(+) T-cell depletion in HIV-associated chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014;190:744–55.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Brune KA, Ferreira F, Mandke P, Chau E, Aggarwal NR, D’Alessio FR, et al. HIV impairs lung epithelial integrity and enters the epithelium to promote chronic lung inflammation. PLoS One. 2016;11:e0149679.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Rosen MJ, Lou Y, Kvale PA, Rao AV, Jordan MC, Miller A, et al. Pulmonary function tests in HIV-infected patients without AIDS. Pulmonary Complications of HIV Infection Study Group. Am J Respir Crit Care Med. 1995;152:738–45.CrossRefPubMedGoogle Scholar
  56. 56.
    Kuhlman JE, Knowles MC, Fishman EK, Siegelman SS. Premature bullous pulmonary damage in AIDS: CT diagnosis. Radiology. 1989;173:23–6.CrossRefPubMedGoogle Scholar
  57. 57.
    Drummond MB, Kirk GD, Astemborski J, Marshall MM, Mehta SH, McDyer JF, et al. Association between obstructive lung disease and markers of HIV infection in a high-risk cohort. Thorax. 2012;67:309–14.CrossRefPubMedGoogle Scholar
  58. 58.
    Lambert AA, Kirk GD, Astemborski J, Mehta SH, Wise RA, Drummond MB. HIV infection is associated with increased risk for acute exacerbation of COPD. J Acquir Immune Defic Syndr. 2015;69:68–74.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Depp TB, McGinnis KA, Kraemer K, Akgün KM, Edelman EJ, Fiellin DA, et al. Risk factors associated with acute exacerbation of chronic obstructive pulmonary disease in HIV-infected and uninfected patients. AIDS. 2016;30:455–63.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Cribbs SK, Lennox J, Caliendo AM, Brown LA, Guidot DM. Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res Hum Retrovir. 2015;31:64–70.CrossRefGoogle Scholar
  61. 61.
    Collini PJ, Bewley MA, Mohasin M, Marriott HM, Miller RF, Geretti AM, et al. HIV gp120 in the lungs of antiretroviral therapy-treated individuals impairs alveolar macrophage responses to pneumococci. Am J Respir Crit Care Med. 2018;197:1604–15.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    DiNapoli SR, Ortiz AM, Wu F, Matsuda K, Twigg HL, Hirsch VM, et al. Tissue-resident macrophages can contain replication-competent virus in antiretroviral-naive, SIV-infected Asian macaques. JCI Insight. 2017;2:e91214.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Lai S, Starke CE, Flynn JK, Vinton CL, Ortiz AM, Mudd JC, et al. SIV infects functionally polarized memory CD4 T cells equivalently in vivo. J Virol. 2019;93.  https://doi.org/10.1128/JVI.02163-18.
  64. 64.
    Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. The microbiome and the respiratory tract. Annu Rev Physiol. 2016;78:481–504.CrossRefPubMedGoogle Scholar
  65. 65.
    Nimmo C, Capocci S, Honeyborne I, Brown J, Sewell J, Thurston S, et al. Airway bacteria and respiratory symptoms are common in ambulatory HIV-positive UK adults: TABLE 1. Eur Respir J. 2015;46:1208–11.CrossRefPubMedGoogle Scholar
  66. 66.
    Beck JM, Schloss PD, Venkataraman A, Twigg H 3rd, Jablonski KA, Bushman FD, et al. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am J Respir Crit Care Med. 2015;192:1335–44.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Twigg HL, Knox KS, Zhou J, et al. Effect of advanced HIV infection on the respiratory microbiome. Am J Respir Crit Care Med. 2016;194:226–35.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Dolmans RAV, Boel CHE, Lacle MM, Kusters JG. Clinical manifestations, treatment, and diagnosis of Tropheryma whipplei infections. Clin Microbiol Rev. 2017;30:529–55.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    • Morris A, Paulson JN, Talukder H, Tipton L, Kling H, Cui L, et al. Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection. Microbiome. 2016;4:38. In a study of microbiome analysis from serial bronchoalveolar lavage samples in nonhuman primates before and after infection with SHIV, half of the monkeys developed COPD over longitudinal follow-up and tended to have more oral bacteria in their BAL microbiota. There was no relationship between the presence of Tropheryma whipplei in BAL and the development of COPD. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Lozupone C, Cota-Gomez A, Palmer BE, Linderman DJ, Charlson ES, Sodergren E, et al. Widespread colonization of the lung by Tropheryma whipplei in HIV infection. Am J Respir Crit Care Med. 2013;187:1110–7.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Qin S, Clausen E, Nouraie SM, Kingsley L, McMahon D, Kleerup E, et al. Tropheryma whipplei colonization in HIV-infected individuals is not associated with lung function or inflammation. PLoS One. 2018;13:e0205065.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Roy RM, Klein BS. Fungal glycan interactions with epithelial cells in allergic airway disease. Curr Opin Microbiol. 2013;16:404–8.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Morris A, Sciurba FC, Lebedeva IP, Githaiga A, Elliott WM, Hogg JC, et al. Association of chronic obstructive pulmonary disease severity and Pneumocystis colonization. Am J Respir Crit Care Med. 2004;170:408–13.CrossRefPubMedGoogle Scholar
  74. 74.
    Morris A, Kingsley LA, Groner G, Lebedeva IP, Beard CB, Norris KA. Prevalence and clinical predictors of Pneumocystis colonization among HIV-infected men. AIDS. 2004;18:793–8.CrossRefPubMedGoogle Scholar
  75. 75.
    Morris A, Alexander T, Radhi S, Lucht L, Sciurba FC, Kolls JK, et al. Airway obstruction is increased in Pneumocystis-colonized human immunodeficiency virus-infected outpatients. J Clin Microbiol. 2009;47:3773–6.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002–4.CrossRefPubMedGoogle Scholar
  77. 77.
    Sato M, Hirayama S, Lara-Guerra H, Anraku M, Waddell TK, Liu M, et al. MMP-dependent migration of extrapulmonary myofibroblast progenitors contributing to posttransplant airway fibrosis in the lung. Am J Transplant. 2009;9:1027–36.CrossRefPubMedGoogle Scholar
  78. 78.
    Cui L, Lucht L, Tipton L, Rogers MB, Fitch A, Kessinger C, et al. Topographic diversity of the respiratory tract mycobiome and alteration in HIV and lung disease. Am J Respir Crit Care Med. 2015;191:932–42.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Shipley TW, Kling HM, Morris A, Patil S, Kristoff J, Guyach SE, et al. Persistent Pneumocystis colonization leads to the development of chronic obstructive pulmonary disease in a nonhuman primate model of AIDS. J Infect Dis. 2010;202:302–12.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Kling HM, Shipley TW, Guyach S, Tarantelli R, Morris A, Norris KA. Trimethoprim-sulfamethoxazole treatment does not reverse obstructive pulmonary changes in Pneumocystis-colonized nonhuman primates with SHIV infection. J Acquir Immune Defic Syndr. 2014;65:381–9.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Foisy MM, Yakiwchuk EMK, Chiu I, Singh AE. Adrenal suppression and Cushing’s syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature. HIV Med. 2008;9:389–96.CrossRefPubMedGoogle Scholar
  82. 82.
    Crim C, Calverley PMA, Anderson JA, Celli B, Ferguson GT, Jenkins C, et al. Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results. Eur Respir J. 2009;34:641–7.CrossRefPubMedGoogle Scholar
  83. 83.
    Brassard P, Suissa S, Kezouh A, Ernst P. Inhaled corticosteroids and risk of tuberculosis in patients with respiratory diseases. Am J Respir Crit Care Med. 2011;183:675–8.CrossRefPubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Department of MedicineUniversity of PittsburghPittsburghUSA
  2. 2.VA Pittsburgh Healthcare SystemPittsburghUSA

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