Understanding the influence of genes, diet and occupation on respiratory health

Andre F.S. Amaral1, Vanessa Garcia Larsen1, Sara De Matteis1, Cosetta Minelli1

1Population Health and Occupational Disease Section,National Heart and Lung Institute, Imperial College London, London, United Kingdom

Recommended reading from the Population Health and Occupational Disease Section; Cosetta Minelli,MD, PhD, Senior Lecturer

Obeidat M, et al.; Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respir Med(1)

Reviewed by Andre F.S. Amaral

Respiratory health is determined by genetic variation and environmental exposures, and a complex interaction between the two. Despite numerous studies on asthma, chronic obstructive pulmonary disease, cystic fibrosis, and other respiratory diseases, we still do not know enough about the molecular mechanisms underlying the normal and pathological development, growth and function of the lungs.

In an attempt to improve the understanding of the molecular mechanisms explaining changes in airflow obstruction, Obeidat and colleagues integrated data from the SpiroMeta-CHARGE genome-wide association study (GWAS) meta-analysis, the Lung expression quantitative trait loci (eQTL) Consortium, and publicly available databases. The aim was to identify genetic variants (single nucleotide polymorphisms, SNPs) associated with either the FEV1 or the FEV1/FVC that act as eQTLs changing the expression level of one or more genes in lung tissue (1). Their goal was also to identify airflow obstruction-related genes which expression could be modified by therapeutic agents.

Of 49 SNPs previously associated with FEV1 and/or FEV1/FVC in GWASs, 22 were identified as eQTLs. One of them (NCR3-rs2857595) seems to regulate the expression of 11 genes. In lung tissue, the genes regulated by these lung function-associated eQTLs were enriched for developmental and inflammatory pathways, whereas in peripheral blood cells they were only enriched for inflammatory pathways. In addition, Obeidat and colleagues identified an mRNA expression signature for airflow obstruction in lung tissue and compared it with the Connectivity Map database (i.e. catalogue of gene-expression data collected from human cells treated with drug candidates and genetic manipulations) to find existing drugs with potential to interfere with the pathogenesis of obstructive lung disease.

Despite its limitations, this study is the first to report large-scale integration of airflow obstruction GWAS findings and lung eQTLs, and it provides significant insight into the potential ‘causal’ genes underlying the association with airflow obstruction. Having said that, there is still a lot to learn about the molecular mechanisms that explain changes in lung function.There are other recent studies using eQTLs to further investigate variants associated withairflow obstruction (2, 3), but despite a recent study on FVC-associated developmental genes and eQTLs (4) there is a paucity of studies on lung volumes and restrictive lung disease. Similarly, little is known on the interaction between genes and lifestyle, dietary and occupational factors affecting the lungs. To improve our understating of these matters, future studies will definitely have to integrate genomic, epigenomic, metabolomic and well-measured exposure data.


1.Obeidat M, Hao K, Bosse Y, Nickle DC, Nie Y, Postma DS, et al. Molecular mechanisms underlying variations in lung function: a systems genetics analysis. Lancet Respir Med 2015;3(10):782-95

2. Hansel NN, Pare PD, Rafaels N, Sin DD, Sandford A, Daley D, et al. Genome-wide association study identification of novel loci associated with airway responsiveness in chronic obstructive pulmonary disease.Am J Respir Cell Mol Biol 2015;53(2):226-34

3. Wain LV, Shrine N, Miller S, Jackson VE, Ntalla I, Soler Artigas M, et al. Novel insights into the genetics of smoking behaviour, lung function, and chronic obstructive pulmonary disease (UK BiLEVE): a genetic association study in UK Biobank.Lancet Respir Med 2015; 3(10): 769–81

4.Minelli C, Dean CH, Hind M, Alves AC, Amaral AFS, Siroux V, et al. Association of Forced Vital Capacity with the Developmental Gene NCOR2. PLoS One 2016;11(2):e0147388

Mehta AJ,et al.; Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study. Am J Clin Nutr(8)

Reviewed by Vanessa Garcia Larsen

Lung function decline is a strong predictor of overall mortality. Diet contains a wealth of components that have been proposed to protect lung function, including flavonoids found in fruits and vegetables. Extensive experimental evidence shows that flavonoids have strong antioxidant and anti-inflammatory properties which can revert or attenuate lung damage. In addition, detectable levels of anthocyanin metabolites have been identified in lung tissue of rats fed with low doses of blueberries (5), further supporting the notion that flavonoids might have a role to play in respiratory health. However, epidemiological evidence exploring this hypothesis in humans is still sparse. Two observational studies have investigated the cross-sectional association between intake of three major subclasses of flavonoids (flavan-3-ols, flavones and flavonols) and lung function in middle aged Europeans (6) and young adults from South America (5). In both studies, the authors found that individuals with the highest quintile of catechin intake had a higher FEV1(6, 7) and FVC (7) compared to those with the lowest intake.

In their article, Mehta and colleagues (8) report the findings of the first longitudinal study to examine whether dietary intake of flavonoids is associated with a slower lung function decline. They investigated this hypothesis in a sample of 839 older adults from the Veterans Affairs Normative Aging Study, whose lung function (FEV1 and FVC) was measured at least twice andup to 5 visits between 1992 and 2008 (n=2623 measurements). In addition to the repeated measurement of lung function, a strength of the study is the use of repeated estimates from a self-reported, validated food frequency questionnaire from whicha representative list of foods rich in flavonoids was obtained, and annual average intake of six major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was derived. Several potential confounders were also included. .

The authors found that individuals with the highest intake of anthocyanins had a statistically significantly slower decline in FEV1 and FVC compared to those in the lowest quartile of intake by 23.6 and 37.3 mL/year, respectively. Although the study findings are not representative of the general population, these results represent an important step towards improving our understanding of the potential of a diet rich in flavonoids, particularly anthocyanins, to reduce lung function decline with aging. From a public health point of view, replicating these findings in adequately designed RCTs could support recommendations to the population to include these foods in their usual diet.


5. Aqil F, Vadhanam MV, Jeyabalan J, Cai J, Singh IP, Gupta RC. Detection of anthocyanins/ anthocyanidins in animal tissues. J Agric Food Chem 2014; 62:3912-8

6. Tabak C, Arts IC, Smit HA, Heederik D, Kromhout D. Chronic obstructive pulmonary disease and intake of catechins, flavonols, and flavones: the MORGEN Study. Am J Respir Crit Care Med 2001; 164:61-64

7. Garcia-Larsen V, Amigo H, Bustos P, Bakolis I, Rona RJ. Ventilatory function in young adults and dietary antioxidant intake. Nutrients 2015; 7:2879-96

8. AJ Mehta, A Cassidy, AA Litonjua, D Sparrow, P Vokonas, J Schwartz. Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study. Am J Clin Nutr 2016; 103:542-50

Tarlo SM,et al.; Evaluation of Occupational and Environmental Factors in the Assessment of Chronic Cough in Adults: A Systematic Review. Chest (11)

Reviewed by Sara De Matteis

Chronic cough has a high global epidemiological burden (9.6% corresponding to 576,839 cases), and seriously impairs quality of life (9). Occupational and environmental risk factors are both important and preventable determinants of respiratory health effects, including chronic cough (10). Several guidelines have recommended including the evaluation of these factors in the assessment of chronic chough in adults. Nevertheless, it is unknown how frequently these recommendations have been applied in routine diagnostic algorithms.

Tarlo and colleagues (11) addressed this important issue by conducting a systematic review of published cough protocols and guidelines with the aim of describing the recommended approach to evaluation of occupational and environmental factors, the frequency of identification of patients with an occupational or environmental cause for chronic cough, and the outcome of such patients.

PubMed, Scopus, and the Cochrane Library were searched for chronic cough guidelines and protocols up to June 2015 and a systematic review was conducted using state-of-the art methods. Among the 28 articles included in the review, 10 general chronic cough guidelines and protocols were identified. Only the three most recent ones, published since 2006, recommended detailed occupational and environmental assessments. One additional cough statement focused entirely on occupational cough. Of the 28cohort studies of patients with chronic cough that specifically noted that they followedguidelines or protocols, none provided details of occupational and environmental assessments. Among these studies, up to 42% of chronic cough cases remained of unexplained origin.

This is the first systematic review aimed to assess how routinely the recommended evaluation of occupational and environmental risk factors is actually applied in diagnostic algorithms for a common respiratory symptom such as chronic cough. Regretfully it is evident that, despite clear recommendations, there is an important under-recognition among healthcare providers of occupational and environmental causes for chronic cough. Several are the potential consequences, both at individual and public health level. The missed diagnosis prevents appropriate management of the otherwise unexplained chronic cough through cessation of exposure to the causal agent. Moreover, lack of recognition of occupational risk factors prevents application of preventive measures at workplace, therefore putting workers at unnecessary risk. Future studies should aim to address efficacy and effectiveness of these recommendations in patients with unexplained chronic cough to provide also a quantitative estimate of the benefits of evaluating occupational and environmental risk factors in routine diagnostic algorithms.


9. Song WJ, Chang YS, Faruqi S, Kim JY, Kang MG, Kim S, Jo EJ, Kim MH, Plevkova J, Park HW, Cho SH, Morice AH. The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J 2015; 45:1479-81

10. Moscato G, Pala G, Cullinan P, Folletti I, Gerth van Wijk R, Pignatti P, Quirce S, Sastre J, Toskala E, Vandenplas O, Walusiak-Skorupa J, Malo JL. EAACI Position Paper on assessment of cough in the workplace. Allergy 2014; 69:292-304

11. Tarlo SM, Altman KW, French CT, Diekemper RL, Irwin RS. Evaluation of Occupational and Environmental Factors in the Assessment of Chronic Cough in Adults: A Systematic Review. Chest 2016; 149:143-60