- PLWH have an increased risk for several non-infectious pulmonary conditions including chronic obstructive pulmonary disease (COPD).
- COPD can present at younger ages in HIV-positive compared to HIV-negative patients and is often more likely to present as the emphysema subtype of COPD
- As in HIV-negative persons, cigarette smoking is a major risk factor for COPD among HIV- positive individuals.
- In the absence of data on the treatment of COPD specifically in the setting of HIV infection, current therapy of COPD in PLWH should follow the management guidelines proposed for the general population.
According to the Global Initiative for Chronic Obstructive Lung Diseases, COPD is “characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposures to noxious particles or gases” . The major risk factor for COPD is cigarette smoking, but occupational and environmental exposures also contribute. Prior bacterial pneumonia and Pneumocystis pneumonia are associated with airflow obstruction on pulmonary function testing , and given their increased incidence in those with HIV, may play an important role in the risk and progression of COPD in HIV-positive persons.
COPD can occur at any CD4 cell count or HIV viral load in HIV-positive persons. However, the risk of COPD was increased in HIV-positive persons with a high viral load (>200,000 copies/ml) after adjusting for antiretroviral therapy (ART) use . COPD may progress more rapidly in HIV-positive persons with poorly controlled HIV. Amongst HIV-positive injection drug users, the rate of decline in the forced expiratory volume in one second (FEV1) and the forced vital capacity (FVC) was accelerated in patients with high HIV viral load (defined as >75,000 copies/ml) and with low CD4 cell count (defined as <100 cells/µl), when compared to patients with better controlled HIV disease and to those without HIV infection .
The diagnosis of COPD should be suspected in patients who have chronic cough or sputum production, dyspnea, and/or exposure to risk factors for the disease . The diagnosis of COPD requires spirometry, preferably with bronchodilator testing to demonstrate persistent airflow limitation; the definition of persistent airflow limitation requires that the ratio of the forced expiratory volume in one second (FEV1) to the forced vital capacity (FVC) be less than 70%; alternatively, an FEV1/FVC that is less than 95% of the lower limit of normal, in association with an FEV1 of less than 80% of predicted can also be used . Among older patients, using a threshold of the FEV1/FVC of less than 95% of the lower limit of normal results in fewer false-positive diagnoses of COPD . Screening spirometry to detect COPD in asymptomatic populations is generally not recommended , although studies have not addressed whether screening is beneficial in PLWH. A preliminary study conducted in one center found that HIV-positive outpatients had a high prevalence of symptoms and exposures consistent with COPD, and approximately one quarter of those who completed screening spirometry were diagnosed with COPD .
In HIV-positive patients with chronic respiratory symptoms, health care providers should obtain spirometry. Complete pulmonary function testing including measurement of diffusing capacity should also be considered, as PLWH s are more likely to have a decrease in diffusing capacity despite relatively normal spirometry . Indeed, HIV-positive persons have an increased risk of a moderately to severely impaired diffusing capacity, defined as <60% predicted normal, compared to uninfected persons after adjusting for smoking and other risk factors [9, 10]. A decreased diffusing capacity suggests the presence of emphysema or other disease processes such as pulmonary arterial hypertension or pulmonary fibrosis that interfere with normal gas exchange within the lung.
In the absence of data on the treatment of COPD specifically in the setting of HIV infection, current therapy of COPD in PLWH should follow the management guidelines proposed for the general population . In the Global Obstructive Lung Disease (GOLD) 2017 guidelines, therapy for COPD is driven by symptoms and history of exacerbations rather than by severity of airflow limitation, which is reflected by the FEV1 % predicted . Symptoms should be assessed using the COPD Assessment Test (CAT) or the Medical Research Council (MRC) Dyspnea score. In general, therapy is initiated for symptomatic COPD patients with inhaled bronchodilators. For patients who have regular symptoms, monotherapy with a long acting inhaled beta-agonist (LABA) or antimuscarinic (LAMA) is recommended; combination therapy with a LABA plus LAMA should be prescribed if symptoms are persistent . Inhaled steroids are generally reserved for patients who have exacerbations . HIV-positive persons may have a greater risk of COPD exacerbation compared to HIV-negative persons, although whether and how to tailor therapy for HIV-positive patients with frequent exacerbations remains uncertain [11, 12]. Thus, roflumilast or azithromycin may be considered for HIV-positive patients who continue to have exacerbations despite use of triple inhaled therapy (LABA, LAMA, ICS) as per COPD guidelines .
Special consideration should be given to a few key aspects of COPD management for PLWH. As with HIV- negative patients, smoking cessation should be prioritized. Phaseolus also be monitored for potential complications and interactions between COPD medications and antiretroviral therapy. Protease inhibitors, particularly ritonavir, can increase systemic levels of inhaled or intranasal fluticasone. Cushing’s syndrome or adrenal suppression may result when corticosteroids are tapered [13, 14]. The use of high-dose inhaled corticosteroids also requires careful monitoring, as inhaled corticosteroids are associated with increased risk of oral candidiasis, bacterial pneumonia [15, 16], and tuberculosis . The regular use of systemic steroids should preferably be avoided. Given the potential complications associated with steroids, additional studies on the efficacy and/or effectiveness and safety of these medications in HIV-positive persons with COPD are needed.
In addition, COPD is associated with several comorbidities that may particularly complicate care of elderly patients. These include cardiovascular disease, muscle wasting, osteoporosis, malnutrition, depression, anxiety and lung cancer . Providers should review vaccination records with their HIV-positive patients to ensure that all patients have received the recommended pneumococcal (both PCV13 and PPSV23) [19, 20] and yearly inactivated influenza vaccine.
PLWH with COPD should be considered for participation in pulmonary rehabilitation programs. Lung disease may be an important determinant contributing to poor physical function in HIV-positive persons. Among HIV-positive Veterans, chronic obstructive lung disease (COPD and/or asthma) was among the top comorbid conditions independently associated with self-reported increased physical disability . Airflow limitation, as reflected by a low FEV1 is also associated with decreased 6-minute walk distance in PLWH [1, 22]. Emphysema, even when only mild, has also been associated with a greater decrease in 6 minute walk distance in HIV-infected compared to uninfected individuals . Reasons why HIV appears to result in greater physical limitation in COPD patients are not well understood, but could be related to concomitant comorbidities, muscle loss, and inflammation associated with HIV.
In studies of HIV -positive persons with COPD, physical functioning is significantly improved with participation in pulmonary rehabilitation programs . In general, pulmonary rehabilitation programs should be prescribed in persons with COPD who are symptomatic, have frequent exacerbations, or who have more severe disease (e.g. an FEV1<50% predicted. Studies support the safety and potential benefit of exercise training in PLWH  although further studies are needed to determine the role and optimal type of exercise training in HIV-positive patients, particularly older patients with concomitant comorbid diseases such as COPD.
By Kristina Crothers, M.D.
Updated May 2017
- Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). 2017.
- Morris AM, Huang L, Bacchetti P, Turner J, Hopewell PC, Wallace JM, et al. Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus-infected persons. The Pulmonary Complications of HIV Infection Study Group. American journal of respiratory and critical care medicine 2000; 162(2 Pt 1):612-616.
- 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(4):309-314.
- 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(8):1303-1311.
- Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med 1999; 159(1):179-187.
- Lin K, Watkins B, Johnson T, Rodriguez JA, Barton MB, Force USPST. Screening for chronic obstructive pulmonary disease using spirometry: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 148(7):535-543.
- Lambert AA, Drummond MB, Kisalu A, Moxley J, Keruly J, Moore RD, et al. Implementation of a COPD Screening Questionnaire in an Outpatient HIV Clinic. COPD 2016; 13(6):767-772.
- 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(6):790-796.
- 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(3):271-278.
- 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(3):284-288.
- Depp TB, McGinnis KA, Kraemer K, Akgun 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(3):455-463.
- 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(1):68-74.
- Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J. Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction. Intern Med J 2005; 35(1):67-68.
- St Germain RM, Yigit S, Wells L, Girotto JE, Salazar JC. Cushing syndrome and severe adrenal suppression caused by fluticasone and protease inhibitor combination in an HIV-infected adolescent. AIDS Patient Care STDS 2007; 21(6):373-377.
- Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356(8):775-789.
- Drummond MB, Dasenbrook EC, Pitz MW, Murphy DJ, Fan E. Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA 2008; 300(20):2407-2416.
- 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(5):675-678.
- Nazir SA, Erbland ML. Chronic obstructive pulmonary disease: an update on diagnosis and management issues in older adults. Drugs Aging 2009; 26(10):813-831.
- Centers for Disease C, Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbidity and mortality weekly report 2012; 61(40):816-819.
- Kim DK, Riley LE, Harriman KH, Hunter P, Bridges CB, Advisory Committee on Immunization P. Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2017. Ann Intern Med 2017; 166(3):209-219.
- Oursler KK, Goulet JL, Leaf DA, Akingicil A, Katzel LI, Justice A, et al. Association of comorbidity with physical disability in older HIV-infected adults. AIDS Patient Care STDS 2006; 20(11):782-791.
- Campo M, Oursler KK, Huang L, Goetz MB, Rimland D, Hoo GS, et al. Association of chronic cough and pulmonary function with 6-minute walk test performance in HIV infection. J Acquir Immune Defic Syndr 2014; 65(5):557-563.
- Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med 2006; 173(12):1390-1413.
- O’Brien K, Nixon S, Tynan AM, Glazier R. Aerobic exercise interventions for adults living with HIV/AIDS. Cochrane Database Syst Rev 2010; (8):CD001796.