Global lung health: the dangers of mild lung function impairment
Authors: Rosa Faner, Alvar Agusti
Journal: The Lancet Global Health (2019)

The relationship between low lung function and increased mortality risk, especially in the context of ageing and exposure to noxious particles and gases, was established several decades ago.1Ashley F Kannel WB Sorlie PD Masson R Pulmonary function: relation to aging, cigarette habit, and mortality.Ann Intern Med. 1975; 82: 739-745Crossref PubMed Scopus (151) Google Scholar, 2Kannel WB Lew EA Hubert HB Castelli WP The value of measuring vital capacity for prognostic purposes.Trans Assoc Life Insur Med Dir Am. 1980; 64: 66-83PubMed Google Scholar, 3Hole DJ Watt GC Davey-Smith G Hart CL Gillis CR Hawthorne VM Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study.BMJ. 1996; 313: 711-716Crossref PubMed Scopus (766) Google Scholar However, it was not until recently that low peak lung function in early adulthood (and thus the vital lung function trajectory that followed, independently of the ageing process) was associated with an increased prevalence, and about a decade earlier incidence, of respiratory and cardiovascular abnormalities, as well as premature death.4Agusti A Noell G Brugada J Faner R Lung function in early adulthood and health in later life: a transgenerational cohort analysis.Lancet Respir Med. 2017; 5: 935-945Summary Full Text Full Text PDF PubMed Scopus (164) Google Scholar, 5Vasquez MM Zhou M Hu C Martinez FD Guerra S Low lung function in young adult life is associated with early mortality.Am J Respir Crit Care Med. 2017; 195: 1399-1401Crossref PubMed Scopus (63) Google Scholar In The Lancet Global Health, MyLinh Duong and colleagues6Duong M Islam S Rangarajan S et al.Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study.Lancet Glob Health. 2019; 7: e613-e623Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar provide further evidence supporting a relationship between impaired lung function and respiratory and cardiovascular abnormalities and death, with data from the prospective urban rural epidemiology (PURE) study—an international study involving 126 359 adults from 628 urban and rural communities located in high-income, middle-income, and low-income countries, thus representing a large and genetically diverse population exposed to a wide variety of environmental risk factors. Participants (aged 35–70 years at enrolment) were followed up for a median period of 7·8 years (IQR 5·6–9·5) to record cardiovascular and respiratory disease events and deaths. Reduced lung function (measured as country-standardised forced expiratory volume in 1 s [FEV1] values) was associated with increased mortality, incident cardiovascular disease, and respiratory hospitalisations. This relationship was present across all levels of impairment of FEV1 (hazard ratio for mortality 1·27 [95% CI 1·18–1·36] for mild, 1·74 [1·60–1·90] for moderate, and 2·54 [2·26–2·86] for severe impairment vs no impairment). Notably, the population-attributable risks for death or cardiovascular disease from mildly to moderately impaired FEV1 (0–2 SDs below the population mean; clinically normal) were greater than those of severe FEV1 impairment (more than 2 SDs below the population mean), contributing substantially more than tobacco use or previous cardiovascular disease to risk. Importantly, this effect was reproduced across different country-income levels, rural and urban communities, and different intercountry risk exposures,6Duong M Islam S Rangarajan S et al.Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study.Lancet Glob Health. 2019; 7: e613-e623Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar which include tobacco smoke and solid-fuel cooking. On the basis of these observations, Duong and colleagues concluded that impaired lung function (in terms of reduced FEV1) is a strong, independent, and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation events.6Duong M Islam S Rangarajan S et al.Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort study.Lancet Glob Health. 2019; 7: e613-e623Summary Full Text Full Text PDF PubMed Scopus (68) Google Scholar These observations raise a number of questions. The first question regards the mechanisms underlying the association between reduced lung function and adverse health outcomes. As noted in our previously published paper,7Agusti A Faner R Lung function trajectories in health and disease.Lancet Respir Med. 2019; (published online Feb 11.)http://dx.doi.org/10.1016/S2213-2600(18)30529-0Summary Full Text Full Text PDF PubMed Scopus (130) Google Scholar there are different lung function trajectories through life, and we propose that these trajectories are determined by a dynamic and probably cumulative set of gene–environment interactions acting across the lifespan of an individual, which are still poorly defined mechanistically. Within this context, these different trajectories have important health consequences, including an earlier prevalence and incidence of cardiovascular morbidities and premature death;7Agusti A Faner R Lung function trajectories in health and disease.Lancet Respir Med. 2019; (published online Feb 11.)http://dx.doi.org/10.1016/S2213-2600(18)30529-0Summary Full Text Full Text PDF PubMed Scopus (130) Google Scholar therefore, the genetic (or genomic) factors that govern the abnormal development of the lung might also be associated with the abnormal development or malfunction of other systemic organs. Accordingly, Horikoshi and colleagues8Horikoshi M Beaumont RN Day FR et al.Genome-wide associations for birth weight and correlations with adult disease.Nature. 2016; 538: 248-252Crossref PubMed Scopus (274) Google Scholar reported that the genetic loci associated with birthweight were also associated with the development of adult cardiovascular and metabolic disease. Further questions, with important health-care implications, arise from the finding that much of the effect on mortality and cardiovascular disease is from FEV1 within the currently accepted normal clinical levels. Should we still consider mild impairment of FEV1 to be within the normal range? Should lung function be routinely tested in early adulthood to identify individuals who are at increased risk and offer them targeted health care; and, if so, how will we be able to promote lung health in these apparently healthy individuals? Finally, how should these findings be translated into practice for public health or clinical practice? We suggest that spirometry—an easy, cheap, and reproducible test—should be used much more often and earlier in order to identify this group of high-risk individuals. In this context, impaired lung function, particularly in early adulthood, should be considered a canary in a coal mine, used to raise the alert for potential future risks.9Bush A Low lung function in young adult life is associated with early mortality.Am J Respir Crit Care Med. 2018; 197: 538-539Crossref PubMed Scopus (9) Google Scholar We declare no competing interests. Mortality and cardiovascular and respiratory morbidity in individuals with impaired FEV1 (PURE): an international, community-based cohort studyFEV1 is an independent and generalisable predictor of mortality, cardiovascular disease, and respiratory hospitalisation, even across the clinically normal range (mild to moderate impairment). Full-Text PDF Open Access