Version May 2024
INTRODUCTION — Chronic obstructive pulmonary disease (COPD) is the result of complex interplay between clinical and molecular (ie, genetic) risk factors [1,2]. These interactions are the reason that two individuals may have identical clinical risk factors, but only one will develop COPD. Identifying risk factors for COPD and better understanding their interactions may lead to strategies that reduce the prevalence of COPD.
Risk factors for COPD and strategies for risk reduction are discussed in this topic review. The clinical manifestations, diagnosis, staging, natural history, and treatment of COPD are reviewed separately. (See "Chronic obstructive pulmonary disease: Diagnosis and staging" and "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions" and "Stable COPD: Initial pharmacologic management".)
LUNG FUNCTION — Lung function normally increases as the lungs grow during childhood and adolescence, peaks shortly after 20 years of age, and then begins to decline gradually (figure 1). Risk factors for chronic obstructive pulmonary disease (COPD) cause one or more abnormal patterns of lung function as shown in the figure (figure 1):
●Reduced lung growth
●Premature lung function decline
●Accelerated lung function decline
Accelerated lung function decline is most common. However, each of these abnormal patterns can reduce lung function to an extent that the individual is considered to have COPD. (See "Chronic obstructive pulmonary disease: Diagnosis and staging".)
CLINICAL RISK FACTORS — Definite risk factors for chronic obstructive pulmonary disease (COPD) include smoking and increased airway responsiveness [3-5]. Environmental exposures (other than smoking), atopy, antioxidant deficiency, and prior tuberculosis may also be risk factors [6]. A taxonomy of COPD types has been proposed based on these risk factors ("etiotypes") (table 1) [1,7].
Environmental exposures
Cigarette smoking — Numerous epidemiologic studies indicate that tobacco smoking is overwhelmingly the most important risk factor for COPD [6,8-14]. As an example, a retrospective cohort study (n = 8045) found that subjects who smoked cigarettes throughout a 25-year observation period were more likely than never smokers to develop COPD (36 versus 8 percent) [11]. In another study, the single best variable for predicting which adults will have airflow obstruction on spirometry is a history of more than 40 pack-years of smoking (positive likelihood ratio [LR], 12 [95% CI, 2.7-50]) [15,16]. However, other data suggest smoking duration may provide stronger risk estimates of COPD than the composite index of pack-years [17]. This may in part be due to increased risk associated with smoking exposure in early adolescence [18].
The presence of additional respiratory symptoms does not appear to increase risk of developing airflow obstruction in current or former smokers with significant tobacco exposure. In one longitudinal cohort of 495 patients aged 40 to 80 years with a more than 20 pack-year smoking history (median 40 pack-years) and preserved spirometry, risk of developing airway obstruction over five years was 30 to 35 percent regardless of the presence of respiratory symptoms [19].
Smoking tobacco through a Chinese water pipe (narghile) is also associated with an increased risk of COPD compared with never smoking (adjusted odds ratio [OR], 10.61; 95% CI, 6.89-16.34), challenging the assumption that filtering the tobacco smoke through water might be protective [20]. Smoking both tobacco and marijuana synergistically increases the risk of COPD and respiratory symptoms [21].
Genetic influences may enhance an individual's susceptibility to the detrimental effects of cigarette smoke. This is supported by an observational study that found that bronchodilator responsiveness (a surrogate measure of risk for accelerated lung function decline) was increased among current or former smokers who had a first-degree relative with severe early-onset COPD, compared to current or former smokers who did not have such a relative [22].
Pollution, biomass, and occupational exposures — Numerous studies indicate that environmental exposure to particulate matter, dusts, vapors, fumes, or organic antigens may also be a risk factor for COPD [6,13,23-38]. As an example, a population-based sample (n = 8515) found that COPD was more common among those exposed to occupational dust than those who were unexposed (odds ratio [OR] 1.5, 95% CI 1.17-2.08) [23]. Another study found that former (but not current) smokers who live in homes estimated to have high levels of indoor small (<2.5 micron) airborne particulate matter (PM2.5) demonstrate accelerated loss of lung function [39]. This finding may in part explain the observation that COPD is more common in women exposed to indoor biomass smoke [29,40,41].
In studies of outdoor environmental pollution, PM2.5 has been most strongly associated with incident COPD [42]. In one meta-analysis of worldwide observational studies using several different pollution exposure estimates, every 10 mcg/m3 increase in PM2.5 level was associated with an 18 percent increase in the incidence of COPD (pooled hazard ratio 1.18, 95% CI 1.13-1.23) [43]. Coarse particulates have often not been found to be strongly associated with COPD in observational studies [43,44]; variable results have been seen for nitrogen dioxide, ozone, and other components of air pollution [43,45,46].
Occupational exposure to chemical disinfectants (eg, glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds) is associated with an increased risk of COPD among nurses; adjusted hazard ratios for high-level exposure range from 1.25 (95% CI 1.04-1.51) to 1.36 (95% CI 1.13-1.64) [47]. In a large biobank study, exposure to pesticides was also associated with COPD, with a prevalence ratio of 1.13 for ever-exposure and 1.32 for heavy-exposure, respectively [48]. However, a large international study of nearly 29,000 individuals from 34 countries (both high and low/middle income) found that working in settings with high exposure to dusts or fumes associated with increased respiratory symptoms, but did not correlate with decreases in postbronchodilator spirometry consistent with COPD [49].
Allergy and asthma
Airway responsiveness — Increased airway responsiveness to allergens or other external triggers is a risk factor for COPD, according to numerous observational studies [50-58]. As an example, one retrospective cohort study (n = 9651) found that the incidence of COPD over 11 years was higher among individuals with increased airway responsiveness, compared to those without increased airway responsiveness (OR 4.5, 95% CI 3.3-6.0) [55].
While it is certain that both airway responsiveness and smoking are independent risk factors for COPD, conflicting data make it unclear whether they interact. While several studies suggest that cigarette smoking increases the effect of airway responsiveness on the development of COPD [59], other studies do not [22,51-54].
Atopy — Atopy may increase an individual's risk for COPD, according to an observational study of 1025 older men (mean age 61 years) without asthma who underwent baseline skin prick and pulmonary function testing and were then followed for a median of three years [60]. Atopy was considered present when there was a mean wheal size ≥2 mm in response to four antigens: house dust, mixed grasses, mixed trees, and ragweed. Atopy predicted an excess annual rate of decline of the FEV1 (9.5 mL per year) and the FEV1/FVC (0.3 percent per year), compared with nonatopic patients. Animal studies provide further support that atopy and COPD are related [61].
Asthma — Mild to moderate persistent asthma is a risk factor for the development of COPD. In a study that utilized the Childhood Asthma Management Cohort (684 participants) to define clinical growth patterns in FEV1 over 18 years of follow-up, the FEV1 growth patterns of reduced growth, early decline, or both reduced growth and early decline were associated with the diagnosis of COPD based on spirometric criteria for airflow limitation (post-bronchodilator FEV1/FVC <0.70) [1,62]. Similarly, In a separate longitudinal population-based cohort with more than 45 years of follow-up, patients with asthma that remitted during childhood or adulthood had modest increases in risk for COPD based on post-bronchodilator airflow limitation in middle age (OR 2.0, 95% CI 1.1-3.6 and 3.6, 95% CI 1.3-10, respectively), whereas those with long-standing asthma had highly elevated risk of meeting these spirometric criteria for COPD (OR 8.7 and 6.7 for childhood-onset and adolescent/adult-onset persistent asthma, respectively) [63].
Abnormal lung development — Bronchopulmonary dysplasia, also known as neonatal chronic lung disease (CLD), is a consequence of preterm birth that is defined by dependence on supplemental oxygen for more than 28 days post-partum. Radiographic emphysema and evidence of airflow limitation on pulmonary function testing have been noted in young adult survivors of moderate and severe bronchopulmonary dysplasia [64,65]. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Obstructive lung disease in adulthood'.)
Infections
Childhood pneumonias — Some patients without environmental exposures but with a history of prior infection demonstrate persistent airflow obstruction [4]. Infections in infancy, particularly respiratory syncytial virus, appear to demonstrate particularly increased risk [66,67]. The suspected mechanism is abnormal repair of injured lung leading to airway and parenchymal distortion in areas of prior infection.
Tuberculosis — Pulmonary tuberculosis may contribute to airflow obstruction via endobronchial infection and subsequent bronchostenosis or via lung parenchymal destruction with loss of airway tethering and is a risk factor for chronic airway obstruction in population studies [6,68]. In a study of 8784 Chinese subjects aged 50 or older, radiographic evidence of prior pulmonary tuberculosis was associated with an increased risk for airflow obstruction, independent of cigarette smoking, biomass fuel exposure, and prior diagnosis of asthma [69]. (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Endobronchial tuberculosis'.)
HIV — With an increase in worldwide use of highly effective antiretroviral therapy, there has been increasing recognition of longer-term complications of HIV infection. One meta-analysis of 11 prevalence studies found that patients living with HIV had an increased risk of developing COPD compared to non-HIV controls (OR 1.14, 95% CI 1.05-1.25) [70]. Prevalence in the population increased with the prevalence of detectable viral load, but not with CD4 count. However, even those who are virally suppressed are likely at higher risk for significant lung function decline over time than the general population, particularly in the setting of concomitant tobacco use [71].
Other risk factors
Sex — Women appear to be more susceptible to developing COPD and emphysema than men [72,73]. In a study that assessed the amount of emphysema by measuring lung attenuation on computed tomography, men and women had a similar amount of emphysema overall, but women had smoked a substantially lower number of pack years [73].
Antioxidant deficiency — There are limited data suggesting that a deficiency of antioxidant vitamins (eg, vitamins C and E) may be a risk factor for COPD [74-76]. In theory, a deficiency of antioxidant vitamins leaves the host unable to defend itself against the destructive effects of oxidative radicals, which derive from both exogenous sources (eg, cigarette smoke) and endogenous sources (eg, lung phagocytes).
As an example, in one prospective cohort study including smokers and former smokers, those in the highest quintile of antioxidant dietary intake (from flavonoids) had reduced risk of developing COPD compared with those in the lowest quintile, even after accounting for smoking exposure, physical activity, socioeconomic status, and other factors (hazard ratio 0.8) [77].
MOLECULAR RISK FACTORS — Observational studies indicate that molecular risk factors for chronic obstructive pulmonary disease (COPD) exist [22,78-81]. As an example, one observational study found that the risk of COPD was approximately three times higher among the first-degree relatives of patients who had severe premature COPD unrelated to alpha-1 antitrypsin deficiency [80]. The role of alpha-1 antitrypsin deficiency in COPD is discussed separately. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency".)
Molecular risk factors for COPD have been assessed using several different methods, including studies of gene polymorphisms, antioxidant enzyme function, metalloproteinase dysregulation, and abnormalities that cause excess elastase.
Gene polymorphisms — Several gene polymorphisms (SNPs) have been identified that may increase the risk of COPD [82-95]. The functions of many of these genes are still unknown. Some examples are listed here:
●Transforming growth factor beta 1 – Transforming growth factor beta is a member of a large superfamily of polypeptides involved in cellular growth, differentiation, and activation. SNPs of the gene encoding transforming growth factor beta 1 have been associated with development of COPD in smokers [85,88,89].
●Serpine2 – Serpine2, also known as serpin peptidase inhibitor, was initially identified based on mouse and human fetal lung gene expression and then assessed in a case control study [96]. Serpine2 appears to be a COPD susceptibility gene that may be influenced by gene-by-smoking interaction.
●Cystic fibrosis transmembrane conductance regulator (CFTR) – Loss of function of the CFTR gene causes cystic fibrosis (CF), but some combinations of deleterious variants can have incomplete penetrance or remain clinically silent. Assessment of coding variants for CFTR in cigarette smokers from two large cohort studies (COPDGene and ECLIPSE) found that the presence of a single CF-causing variant was associated with chronic bronchitis [97]. Additionally, the small number of subjects with two or more CFTR variants on separate alleles had significantly higher incidence of COPD than the cohort as a whole.
●Other loci from genome-wide association studies – Genome-wide association studies (GWAS) have identified more than 80 separate loci associated with COPD or related disease. Notable loci include:
•The earliest identified sites associated with COPD were 15q25 (CHRNA3/CHRN5/IREB2) [90], 4q31 (near HHIP) [91,92], and 4q22 (FAM13A) [93].
•Notable additional loci associated with COPD were identified at 19q13 (near CYPA6, a locus also associated with cigarette smoking) [94], 5q32 (near the gene for 5-hydroxytryptamine receptor 4 [HTR4], a locus also associated with lung function in the general population) [86], as well as 6p21 (AGER) [98], and 14q32 (RIN3) [99].
•Several more loci have been associated with chronic bronchitis (11p15.5 [EFCAB4A, CHID1, APA2A2]) [100] and airway hyper-responsiveness in COPD (9p21.2 near Lingo2, 3q13.1 near MyH15, and 5q33 near the sarcoglycan delta [SGCD] gene) [101]. While COPD lags behind asthma in terms of GWAS-identified loci are concerned, the gap is narrowing.
•A separate GWAS was performed in a population based cohort (Multi-Ethnic Study of Atherosclerosis [MESA]-SNP Health Association Resource [SHARe]) in the United States and found two SNPs associated with the percentage of lung emphysema determined by computed tomography [102]. In addition, genes related to alpha-mannosidase appeared to be associated with the ratio of upper to lower lobe emphysema in some ethnic groups.
At least four of the loci associated with COPD overlap with idiopathic pulmonary fibrosis, with the two diseases having allelic effects in opposite directions, possibly indicating a molecular switch at that genetic locus [103].
A polygenic risk score developed using a lung function-based GWAS strongly associates with the likelihood of COPD in multiple cohorts of European ancestry [104], and higher polygenic risk scores may help identify patients at risk for early incident COPD [105].
Antioxidant related enzymes — Genetic variation in antioxidant enzyme function or regulation may affect risk for COPD [106]. In particular, the genes for glutathione S-transferases P1 and M1, glutamate cysteine ligase, and superoxide dismutase appear to be involved. Gene association studies are not available for some other antioxidant enzymes (eg, thioredoxin, gamma-glutamyl transferase) that may turn out to be important.
●Glutathione S-transferases – Glutathione S-transferase P1 (GSTP1) aids in the detoxification of a number of substances that are found in cigarette smoke. Decreased glutathione S-transferase P1 activity due to genetic polymorphisms may increase the frequency of COPD [107-109]. Several case-control studies have identified a specific polymorphism in exon 5 (Ile105Val) that is more common among persons with COPD than controls [108,110]. Homozygous deletion of glutathione S-transferase M1 (GSTM1) has been associated with increased COPD risk in some, but not all studies [85,106,107,110].
●Glutamate cysteine ligase – Glutamate cysteine ligase (GCL) is one of the three enzymes that relate to glutathione synthesis. Genetic variants in the promoter region and in the catalytic subunit that cause decreased glutathione levels have been associated with and increase risk of COPD [106,111].
Metalloproteinase dysregulation — Matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes that degrade extracellular matrix proteins. The activity of MMPs is regulated by tissue inhibitors of metalloproteinase (TIMPs). Numerous observational studies have demonstrated an association between COPD and abnormal activity of certain MMP or TIMP subtypes [112-116]:
●A case-control study compared the bronchoalveolar lavage fluid of patients with emphysema to normal controls [113]. Patients with emphysema had increased MMP-1 (collagenase-1) expression and absent MMP-12 (macrophage elastase) activity [113].
●Sputum from patients with asthma and COPD has increased MMP-2 (gelatinase A), MMP-9 (gelatinase B), MMP-8 (Collagenase 2), and TIMP-1 activity, compared to controls [114,116]. In addition, patients with stable COPD have an increased concentration of serum TIMP-1, compared to controls and patients with stable asthma [117].
●MMP-12 has been identified as a gene associated with reduced lung function in asthma and early decline in lung function in COPD [118,119]. This gene has been associated with emphysema in mouse models of COPD [120].
The relationships among MMPs, TIMPs, and COPD are an area of ongoing research, with MMP inhibitors under investigation as therapeutic agents for COPD [112,121,122].
Excess elastase — The possibility that excess elastase contributes to COPD is suggested by two principal observations:
●Premature emphysema is associated with deficiency of alpha-1 antitrypsin, an inhibitor of neutrophil elastase. (See "Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency".)
●Macrophage elastase-deficient mice do not develop emphysema despite intense, long-term exposure to cigarette smoke [120]. This is true even if excess inflammatory cells are attracted to the lung with exogenously administered monocyte chemoattractant protein-1.
RISK REDUCTION — Most of the clinical risk factors for chronic obstructive pulmonary disease (COPD) can be modified. However, it is difficult to directly measure the impact of risk factor modification on the incidence of COPD because of the extended duration between exposure to the risk factor and the onset of measurable airway obstruction. Studies need to be conducted over several decades for direct measurement.
As an alternative approach, most studies determine the rate of lung function decline and use it as an indirect measure of the risk of developing COPD. The goal of risk factor modification is to mitigate lung function decline, since patients with increased lung function decline are more likely to develop COPD. (See 'Lung function' above.)
Indirect evidence suggests that smoking cessation has the greatest impact on preventing COPD. Physical activity and avoidance of inhalational exposures may also reduce the incidence of COPD. Anti-inflammatory therapy and antioxidant therapy have been studied but appear to have minimal impact on the development of COPD.
Smoking cessation — Smoking cessation reduces the accelerated decline in lung function that is associated with smoking, which decreases the likelihood that COPD will develop [11,123,124].
This was illustrated by a retrospective cohort study (n = 8045) that found the incidence of COPD over 25 years was less among patients who had never smoked or quit smoking than among patients who continued to smoke [11]. Specifically, the incidence of COPD among never smokers, smokers who quit prior to the study, smokers who quit during the initial five years of the study, smokers who quit 5 to 15 years into the study, smokers who quit 15 to 25 years into the study, and those who continued to smoke was 4, 12, 5, 14, 24, and 41 percent, respectively among men. The incidence was 9, 11, 20, 25, 29, and 31 percent, respectively, among women.
Additional benefits of smoking cessation, as well as risks and approaches are discussed separately. (See "Benefits and consequences of smoking cessation" and "Overview of smoking cessation management in adults" and "Behavioral approaches to smoking cessation".)
Exposure avoidance — Reduction of environmental exposure to particulate matter, dusts, gases, vapors, fumes, or organic antigens is associated with slower lung function decline, but to a much smaller degree than smoking cessation.
This was demonstrated by a retrospective cohort study (n = 9651), which found that decreased particulate matter concentration was associated with a small reduction of the annual rate of decline of the forced expiratory volume in one second (FEV1) over 11 years [125]. Specifically, a 10 mcg per m3 annual decrease in the concentration of particulate matter was associated with a 3 mL reduction of the annual decrease of FEV1. This effect is small and of limited clinical relevance to individual patients, but may have public health relevance [126].
In a nine-year prospective cohort study, improved kitchen ventilation and/or use of biogas instead of biomass fuel were associated with a reduced decline in FEV1 [127]. When both interventions were utilized, the decline in FEV1 was decreased by 16 mL/year (95% CI 9-23 mL/year).
A variety of strategies are available to reduce the burden of inhaled particles, gases, vapors, and fumes [1,127]:
●Implement, monitor, and enforce strict control of airborne exposure in the workplace
●Initiate intensive and continuing education of workers, managers, clinicians, and legislators
●Promote smoking cessation since smoking aggravates exposure to other particles and gases
●Improve ventilation in areas where biomass fuels are used for cooking and promote use of clean fuels
Physical activity — Physical activity may mitigate lung function decline in active smokers. In a retrospective cohort study, 6790 volunteers were followed for a median duration of 11 years [128]. Active smokers with a moderate to high level of physical activity were less likely to develop COPD than active smokers with a low level of physical activity (OR 0.77, 95% CI 0.61-0.97). Additional studies are necessary before physical activity can be recommended as a means of decreasing the incidence of COPD.
Anti-inflammatory therapy — The observation that increased airway responsiveness is a risk factor for COPD led to the hypothesis that anti-inflammatory therapy may mitigate accelerated lung function decline.
●Inhaled glucocorticoids – The use of inhaled glucocorticoids in young adults to prevent the onset of COPD has not been studied. However, the impact of inhaled glucocorticoids on lung function decline in patients with established COPD has been extensively studied and is discussed separately. (See "Role of inhaled glucocorticoid therapy in stable COPD".)
●Statins – Statins (hydroxymethylglutaryl [HMG] CoA reductase inhibitors) are generally used for their lipid lowering characteristics, but also appear to have anti-inflammatory properties. In observational studies of COPD [129-131], statins have been associated with a lower rate of decline in pulmonary function, reduced rate and severity of exacerbations, rate of hospitalizations, and mortality. However, in a randomized trial that compared simvastatin with placebo in 885 patients with COPD, simvastatin did not attenuate lung function decline or reduce exacerbations. These studies are described in greater detail separately. (See "COPD exacerbations: Prognosis, discharge planning, and prevention", section on 'Ineffective interventions'.)
The effect of other anti-inflammatory therapies (eg, nonsteroidal anti-inflammatory drugs, systemic glucocorticoids) has not been studied in relevant patient populations.
(N) acetylcysteine — (N) acetylcysteine is a thiol derivative that has potential antioxidant and mucoactive effects. These effects have been explored in patients with COPD with conflicting results, and systematic reviews have found little or no benefit on the reduction in exacerbations or quality of life. (See "Role of mucoactive agents and secretion clearance techniques in COPD", section on 'Thiols and thiol derivatives'.)
The impact of antioxidant therapy (eg, (N) acetylcysteine) on lung function decline was studied in response to observations that antioxidant deficiency may be a risk factor for COPD. A trial that randomly assigned 50 patients with COPD to receive (N) acetylcysteine (600 mg/day) or placebo for three years found no between group difference in the annual rate of lung function decline [132]. Similarly, in a study that used a higher dose of (N) acetylcysteine (1200 mg/day) in 120 patients with COPD, no difference was found in the rate of decline in FEV1, although a slight reduction in the rate of exacerbations was noted in the (N) acetylcysteine group [133]. These studies are described in greater detail separately. (See "Role of mucoactive agents and secretion clearance techniques in COPD", section on 'Thiols and thiol derivatives'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic obstructive pulmonary disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Chronic bronchitis (The Basics)")
●Beyond the Basics topics (see "Patient education: Chronic obstructive pulmonary disease (COPD) (Beyond the Basics)" and "Patient education: Chronic obstructive pulmonary disease (COPD) treatments (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●COPD results from complex interactions between clinical and molecular (ie, genetic) risk factors. (See 'Introduction' above.)
●Definite or possible risk factors for COPD include inhalational exposure (eg, smoking), increased airway responsiveness, atopy, and antioxidant deficiency. (See 'Clinical risk factors' above.)
●Molecular risk factors for COPD include a variety of gene polymorphisms, antioxidant related enzyme dysfunction, metalloproteinase dysregulation, and abnormalities that cause excess elastase. (See 'Molecular risk factors' above.)
●Some of the clinical risk factors for COPD can be modified, thereby reducing the rate of lung function decline. (See 'Risk reduction' above.)
•Smoking cessation is the most important way to reduce the rate of lung function decline and the risk of developing COPD among those who smoke. (See 'Smoking cessation' above.)
•Whenever possible, environmental exposure to particulate matter, dusts, gases, vapors, and fumes should be avoided or reduced. (See 'Exposure avoidance' above.)
•Physical activity may mitigate lung function decline, although further studies are needed. (See 'Physical activity' above.)
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