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Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV,) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV, values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV, 2.75 L) to create the individualized prediction equations. There was significant between individual variability in the rate of FEV, decline, with the interval for the annual rate of decline that contained 95% of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study--ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study--ClinicalTrials.gov, no. NCT00751660, Chronic obstructive pulmonary disease (COPD) is a global health burden that affects 300 million people worldwide (1) resulting in more than 3 million deaths annually. (1,2) Although COPD is defined [...]

Background: Inhaled corticosteroids (ICSs) and long-acting [[beta].sub.2-] agonists (LABAs) are used to treat moderate to severe chronic obstructive pulmonary disease (COPD). Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD. Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847) Setting: 2 university medical centers in The Netherlands. Patients: 114 steroid-naive current or former smokers with moderate to severe COPD. Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months. Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 [micro]g twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 [micro]g twice daily, and salmeterol, 50 [micro]g twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29). Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal [CD3.sup.+] cells (-55% [95% Cl, -74% to -22%]; P = 0.004), [CD4.sup.+] cells (78% [Cl, -88% to 60%]; P < 0.001), [CD8.sup.+] cells (-57% [Cl, -77% to -18%]; P = 0.010), and mast cells (-38% [Cl, -60% to -2%]; P= 0.039) and reduced hyperresponsiveness (P= 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in [FEV.sub.1] decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of [CD3.sup.+] cells (120% [Cl, 24% to 289%]; P = 0.007), mast cells (218% [Cl, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved [FEV.sub.1] level. Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months. Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects. Primary Funding Source: Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center.

Introduction: β-Blockers are known to worsen FE[V.sub.1] and airway hyperresponsiveness (AHR) in patients with asthma. Both characteristics determine the outcome of COPD, a disease with frequent cardiac comorbidity requiring β-blocker [...]

The Dutch hypothesis, formulated in the 1960s, holds that the various forms of airway obstruction are different expressions of a single disease entity. It suggests that genetic factors (eg, airway [...]

One of the major goals of bronchodilator therapy in patients with COPD is to decrease airflow limitation in the airways and, as a consequence, improve dyspnea and exercise tolerance. The [...]

Objectives: Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long [...]

Background: In recent years, fiberoptic bronchoscopy has been introduced successfully in the research of bronchial asthma. Bronchial biopsy specimens obtained by this procedure are small, and an optimal biopsy technique [...]

Background: The institution of inhaled corticosteroids is generally advocated for effective treatment of patients with asthma. It is yet unknown what is the best time to start inhaled corticosteroid therapy [...]

Study objective: To determine the effectiveness of treatment with corticosteroids in patients with COPD. Methods: In this study, we investigated the effect of a 2-year treatment with corticosteroids on clinical [...]

Aim: In this study, the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program (HRP) are compared with those of a 12-week home-care rehabilitation program (HCRP) in COPD patients. A [...]

Background: Some patients with chronic obstructive pulmonary disease may share the clinical characteristics of those with asthma; their disease is sometimes called 'asthmatic bronchitis.' Whether there is a difference between asthmatics who do and do not develop chronic bronchitis is not yet clear. We investigated whether asthma and chronic bronchitis may share some 'allergic' phenotypes and whether asthmatic individuals who develop chronic bronchitis subsequently have steeper declines in lung function. Methods: Known risk factors for decline in lung function were analyzed in a representative community population of adults followed up longitudinally since 1972 in Tucson, Ariz, in groups with persistent, newly developed, and past diagnoses of asthma and chronic bronchitis. We evaluated contributions of initial level of forced expiratory volume in 1 second (FE[V.sub.1]), reversibility with isoproterenol hydrochloride nebulized aerosol bronchodilator treatment, percentage of blood eosinophils to determine eosinophilia, and IgE level. Results: The concurrence of chronic bronchitis and asthma is associated with a steeper decline in FE[V.sub.1] than is asthma as the sole diagnosis. Asthmatics (those with persistent asthma with and without chronic bronchitis) had the greatest prevalence of increased reversibility with isoproterenol therapy and with eosinophilia. The prevalence of eosinophilia was also high in those with newly diagnosed chronic bronchitis without asthma; however, this was not the case in those with persistent chronic bronchitis without asthma. Larger bronchodilator responses were related to steeper declines in FE[V.sub.1], both in persistent asthma and in chronic bronchitis. Conclusions: Bronchodilator response and eosinophilia are generally believed to be hallmarks of asthma. We show that these characteristics may be present in chronic bronchitis as well. The presence of a large (>25%) bronchodilator response is associated with a steeper decline in FE[V.sub.1].

The validity of peak inspiratory mouth pressure (P.PI-max) as a measure of inspiratory muscle strength was investigated by comparing it with sniff Pes in patients with COPD with respect to [...]

The effect of breathing with a positive expiratory pressure of 5 cm [H.sub.2]O was investigated in eight patients with COPD (mean [SD] [FEV.sub.1] = 54 [13] percent predicted). Specific work [...]

Slow inspiratory vital capacity (IVC) and forced expiratory volume in 1 s (FE[V.sub.1]) before and after an inhaled β-agonist are widely used to detect reversible airflow limitation in patients with [...]

PURPOS: The purpose of this study was to investigate whether systemic lupus erythematosus (SLE) patients with interstitial lung disease represent a particular subset of patients characterized by the presence of clinical, serelogic, and nailfold capillary patterns overlapping scleroderma. PATIENTS AND METHODS: In 57 consecutive patients with SLE, a standardized detailed history was obtained and a physical examination performed, directed at signs and symptoms of connective tissue diseases, in particular scleroderma. Additionally, pulmonary function testing, chest radiography, radionuclide transit studies of the esophagus, nailfold capillary microscopy, and detailed serelogic studies directed at the antigenic specificities of antinuclear antibodies were performed. Patients were divided into three groups based on the results of pulmonary function testing, ie., normal lung function, restriction, or isolated impairment of diffusion. Clinical, serologic, and nailfold capillary microscopic Findings were compared among these three groups. RESULTS: Twenty patients had normal lung function, 19 had restrictive lung function loss, and 9 had an isolated impairment of the diffusing capacity ([T.sub.1]co). Patients with obstructive lung disease (n: 9) were excluded from analysis. Sclerodermatous changes of the hands were associated with a restrictive lung function pattern. Interstitial changes on chest radiograph were associated with isolated impairment of [T.sub.1],co. Nailfold capillary abnormalities correlated with decreased [T.sub.1],co and Dm, the component of [T.sub.1],co representing the diffusing capacity of the alveolocapillary membrane. Antibodies to U1-RNA were associated with restrictive lung function and decreased [T.sub.1],co. CONCLUSION: We conclude that interstitial lung disease is present in a subset of SLE patients characterized by an increased prevalence of selerederma traits and anti-(U1)RNA antibodies. Microvascular changes may contribute to the development of interstitial lung disease in SLE as well as in scleroderma

Hyperresponsiveness of the bronchial airways is a fundamental characteristic of a number of respiratory disorders, including asthma and chronic obstructive pulmonary disease (COPD). In general, the degree of airway hyperresponsiveness correlates with the severity of the symptoms reported by patients suffering from these diseases. However, in some cases, the degree of airway hyperresponsiveness does not seem to be predictable on the basis of symptom severity. To further characterize the relationships between airway hyperresponsiveness, respiratory symptoms, and peak expiratory flow (PEF; an index of the maximum amount of gas breathed out from the lungs), a study was carried out with 221 hyperresponsive patients with moderately severe airway obstruction. The patients were categorized as having asthma (81 patients), asthmatic bronchitis (69 patients), or chronic obstructive pulmonary disease (44 patients). Twenty-seven patients could not be accurately classified into one of these groups. Airway responsiveness was quantified by measuring the degree of bronchial constriction in response to inhaled histamine (a bronchoconstrictor substance). Average airway responsiveness was significantly higher in asthmatic patients than in either COPD or asthmatic bronchitis patients, but there was a large amount of variability in all three groups. Airway responsiveness was moderately correlated with peak expiratory flow; however, for each level of airway responsiveness, there was wide variability in the PEF values obtained, indicating that the two measures are not interchangeable. Symptom severity was weakly related to airway responsiveness and PEF levels. Hence, all three variables (airway hyperresponsiveness, peak expiratory flow, and symptom severity) appear to provide related but different information on the underlying disease process. (Consumer Summary produced by Reliance Medical Information, Inc.)

Background/objective: In general, smoking cessation programs have low success rates. We evaluated the effectiveness of a 1-year smoking cessation program. This program was part of a research project investigating the [...]

Translation of genomic alterations to protein changes in chronic obstructive pulmonary disease (COPD) is largely unexplored. Using integrated proteomic and RNA sequencing analysis of COPD and control lung tissues, we identified a protein signature in COPD characterised by extracellular matrix changes and a potential regulatory role for SUMO2. Furthermore, we identified 61 differentially expressed novel, non-reference, peptides in COPD compared with control lungs. This included two peptides encoding for a new splice variant of SORBS1, of which the transcript usage was higher in COPD compared with control lungs. These explorative findings and integrative proteogenomic approach open new avenues to further unravel the pathology of COPD.

A Patient initially presented with sarcoidosis in combination with myositis of sarcoid origin and Raynaud's phenomenon. During the course of his disease, he additionally developed scleroderma. Bronchoalveolar lavage, performed because [...]

Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma.

Study objectives: The influence of bronchiolitis obliterans syndrome (BOS) on costs after lung transplantation was investigated by comparing the costs of patients with and without this condition. Design: Follow-up costs [...]

(CHEST 2000; 117:285S) Abbreviations: AMP = adenosine 5'-monophosphate; BHR = bronchial hyperresponsiveness COPD is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may yield information about airway inflammation, and [...]

(CHEST 2000; 117:262S) Abbreviation: ECP = eosinophil cationic protein Inflammation in the airways in COPD is largely attributed to smoking, yet this may be present even in ex-smokers. We studied [...]

Chronic obstructive pulmonary disease (COPD) is a major health burden in adults and cigarette smoking is considered the most important environmental risk factor of COPD. Chromosome 15q25.1 locus is associated with both COPD and smoking. Our study aims at understanding the mechanism underlying the association of chromosome 15q25.1 with COPD through epigenetic and transcriptional variation in a population-based setting. To assess if COPD-associated variants in 15q25.1 are methylation quantitative trait loci, epigenome-wide association analysis of four genetic variants, previously associated with COPD (P< 5 × 10−8) in the 15q25.1 locus (rs12914385:C>T-CHRNA3, rs8034191:T>C-HYKK, rs13180:C>T-IREB2and rs8042238:C>T-IREB2), was performed in the Rotterdam study (n= 1489). All four variants were significantly associated (P< 1.4 × 10−6) with blood DNA methylation of IREB2, CHRNA3and PSMA4, of which two, including IREB2and PSMA4, were also differentially methylated in COPD cases and controls (P< 0.04). Further additive and multiplicative effects of smoking were evaluated and no significant effect was observed. To evaluate if these four genetic variants are expression quantitative trait loci, transcriptome-wide association analysis was performed in 1087 lung samples. All four variants were also significantly associated with differential expression of the IREB23’UTR in lung tissues (P< 5.4 × 10−95). We conclude that regulatory mechanisms affecting the expression of IREB2gene, such as DNA methylation, may explain the association between genetic variants in chromosome 15q25.1 and COPD, largely independent of smoking.

IntroductionCOPD is a chronic, progressive, inflammatory disease of the lungs and the third leading cause of death worldwide. The current knowledge of the pathophysiology of COPD is limited and novel insights in underlying disease mechanisms are urgently needed. Since there are clear parallels between ageing and COPD, we investigated genes underlying lung ageing in general and abnormal lung ageing in COPD.MethodsWhole genome mRNA profiling was performed on lung tissue samples (n=1197) and differential gene expression with increasing age was analysed using an adjusted linear regression model. Subsequent pathway analysis was performed using GeneNetwork and the gene-expression signature was compared with lung ageing in the Genotype-Tissue Expression (GTEx) project. In a subset of patients with COPD (n=311) and non-COPD controls (n=270), we performed an interaction analysis between age and COPD to identify genes differentially expressed with age in COPD compared with controls, followed by gene set enrichment pathway analysis.ResultsWe identified a strong gene-expression signature for lung ageing with 3509 differentially expressed genes, of which 33.5% were found nominal significant in the GTEx project. Interestingly, we found EDA2Ras a strong candidate gene for lung ageing. The age*COPD interaction analysis revealed 69 genes significantly differentially expressed with age between COPD and controls.ConclusionsOur study indicates that processes related to lung development, cell-cell contacts, calcium signalling and immune responses are involved in lung ageing in general. Pathways related to extracellular matrix, mammalian target of rapamycin signalling, splicing of introns and exons and the ribosome complex are proposed to be involved in abnormal lung ageing in COPD.

ObjectivesOccupational pesticide exposure is associated with a wide range of diseases, including lung diseases, but it is largely unknown how pesticides influence airway disease pathogenesis. A potential mechanism might be through epigenetic mechanisms, like DNA methylation. Therefore, we assessed associations between occupational exposure to pesticides and genome-wide DNA methylation sites.Methods1561 subjects of LifeLines were included with either no (n=1392), low (n=108) or high (n=61) exposure to any type of pesticides (estimated based on current or last held job). Blood DNA methylation levels were measured using Illumina 450K arrays. Associations between pesticide exposure and 420 938 methylation sites (CpGs) were assessed using robust linear regression adjusted for appropriate confounders. In addition, we performed genome-wide stratified and interaction analyses by gender, smoking and airway obstruction status, and assessed associations between gene expression and methylation for genome-wide significant CpGs (n=2802).ResultsIn total for all analyses, high pesticide exposure was genome-wide significantly (false discovery rate P<0.05) associated with differential DNA methylation of 31 CpGs annotated to 29 genes. Twenty of these CpGs were found in subjects with airway obstruction. Several of the identified genes, for example, RYR1, ALLC, PTPRN2, LRRC3B, PAX2and VTRNA2-1, are genes previously linked to either pesticide exposure or lung-related diseases. Seven out of 31 CpGs were associated with gene expression levels.ConclusionsWe show for the first time that occupational exposure to pesticides is genome-wide associated with differential DNA methylation. Further research should reveal whether this differential methylation plays a role in the airway disease pathogenesis induced by pesticides.

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

Despite the recent explosive rise in number of genetic markers for complex disease traits identified in genome-wide association studies, there is still a large gap between the known heritability of these traits and the part explained by these markers. To gauge whether this ‘heritability gap’ is closing, we first identified genome-wide significant SNPs from the literature and performed replication analyses for 32 highly relevant traits from five broad disease areas in 13 436 subjects of the Lifelines Cohort. Next, we calculated the variance explained by multi-SNP genetic risk scores (GRSs) for each trait, and compared it to their broad- and narrow-sense heritabilities captured by all common SNPs. The majority of all previously-associated SNPs (median=75%) were significantly associated with their respective traits. All GRSs were significant, with unweighted GRSs generally explaining less phenotypic variance than weighted GRSs, for which the explained variance was highest for height (15.5%) and varied between 0.02 and 6.7% for the other traits. Broad-sense common-SNP heritability estimates were significant for all traits, with the additive effect of common SNPs explaining 48.9% of the variance for height and between 5.6 and 39.2% for the other traits. Dominance effects were uniformly small (0–1.5%) and not significant. On average, the variance explained by the weighted GRSs accounted for only 10.7% of the common-SNP heritability of the 32 traits. These results indicate that GRSs may not yet be ready for accurate personalized prediction of complex disease traits limiting widespread adoption in clinical practice.

Targeting small airway inflammation could lead to improved clinical outcomes in asthma. Previous observational studies concluded that therapy with extrafine-particle [mass median aerodynamic diameter (MMAD) <2 µm] inhaled corticosteroids (ICS) is associated with similar or better odds of achieving asthma control at lower prescribed doses than fine-particle ICS (MMAD = 2–5 µm). However, while it is believed that the dose–response for ICS reaches a plateau at sub-maximal doses, it is not clear whether such a plateau occurs with extrafine-particle ICS. To evaluate the potential effect of ICS particle size on dose–response of asthma-related outcomes, we studied severe exacerbation rates in a historical patient cohort of UK adults and adolescents with asthma initiating extrafine- or fine-particle ICS. We extracted electronic medical record data centralized at primary care practices, where information from secondary care and hospitalizations is also aggregated. Data were collected over one baseline (pre-initiation) and one outcome year. Of 32,235 patients with asthma (aged 12–80 years), 54% initiated ICS with extrafine-particle ICS and 46% with fine-particle ICS. Overall, mean age (SD) was 41 (17) years; 60% female; 24% current and 20% ex-smokers. We found a greater (P< 0.001) reduction in exacerbation rate at higher as compared with lower doses of extrafine-particle ICS: for patients initiating on ≤125 µg/day the reduction was −0.016 (95% CI −0.038, 0.006) exacerbations per year and for those initiating on >250 µg/day the reduction was −0.072 (−0.095, −0.049). No significant dose–response relationship was observed for patients initiating on fine-particle ICS [reduction in exacerbations per year: −0.041 (−0.070, −0.012) at the lowest doses and 0.009 (−0.017, 0.036) at the highest, P= 0.856, despite similar exacerbation rates in the baseline period for both cohorts (P= 0.40)]. Our findings suggest that extrafine-particle ICS is associated with a reduction in exacerbation rates in a dose-dependent fashion in an adult asthma population. This dose–response relationship was not observed with fine-particle ICS. ENCePP Trial Registration: EUPAS8840.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10−6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Asthma is a chronic inflammatory disorder of the airways. This chronic inflammation is responsible for increased airways hyperresponsiveness to a variety of stimuli and for the recurrent symptoms and airflow [...]

Data from different healthcare systems on relative cost-effectiveness of asthma step-up therapy strategies are required to inform decision-makers and clinicians. Our objective was to compare cost-effectiveness from the United Kingdom National Health Service perspective of three step-up strategies for patients with asthma uncontrolled by inhaled corticosteroid (ICS) monotherapy. This was a historical matched cohort cost-effectiveness analysis of anonymized medical records for patients with asthma of age 12–80 years. We conducted two-way comparisons of step-up therapy using increased dose (≥50%) of extrafine-particle ICS or add-on long-acting β2-agonist (LABA) via fixed-dose combination (FDC) ICS/LABA inhaler or via separate inhaler. The incremental cost-effectiveness ratio (ICER) was calculated using asthma-related direct costs during one outcome year and a composite measure of risk-domain asthma control (no asthma-related hospital attendance, acute oral corticosteroids, or consultation for lower respiratory tract infection). Patients prescribed ICS dose step-up (n= 3036) had significantly lower baseline-adjusted, mean asthma-related healthcare costs during the outcome year than those prescribed FDC ICS/LABA (n= 3036; mean difference, £124/year). ICS dose step-up had 56% probability of being less costly and marginally less effective (a trade-off), with ICER of £51,449 per additional patient controlled with FDC; and ICS dose step-up had 44% probability of being the preferred treatment strategy (less costly and more effective). In a second comparison, ICS step-up (n= 3232) had 100% probability of being cheaper and more effective than adding LABA to ICS via separate inhalers (n= 6464). For asthma step-up therapy, increasing ICS dose using extrafine-particle ICS is significantly less costly from the payer perspective and marginally (non-significantly) less effective than FDC ICS/LABA therapy containing standard fine-particle ICS. These findings apply primarily to the UK healthcare system but warrant consideration when developing guidelines in settings with strong economic constraints. ClinicalTrials.gov identifier: NCT01697722. Teva Pharmaceuticals Limited, Petach Tikva, Israel.

Previous published analyses have focused on the effect of air pollution on asthma and rhinoconjunctivitis throughout early and middle childhood. However, the role of exposure to air pollution in the development of childhood and adolescent asthma and rhinoconjunctivitis remains unclear. We aimed to assess the longitudinal associations between exposure to air pollution and development of asthma and rhinoconjunctivitis throughout childhood and adolescence.

Lung function measures reflect the physiological state of the lung, and are essential to the diagnosis of chronic obstructive pulmonary disease (COPD). The SpiroMeta-CHARGE consortium undertook the largest genome-wide association study (GWAS) so far (n=48 201) for forced expiratory volume in 1 s (FEV1) and the ratio of FEV1to forced vital capacity (FEV1/FVC) in the general population. The lung expression quantitative trait loci (eQTLs) study mapped the genetic architecture of gene expression in lung tissue from 1111 individuals. We used a systems genetics approach to identify single nucleotide polymorphisms (SNPs) associated with lung function that act as eQTLs and change the level of expression of their target genes in lung tissue; termed eSNPs.

Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

We previously observed that 30 months of inhaled corticosteroid (ICS) treatment can attenuate FEV1decline in COPD, but it is unclear whether withdrawal induces a relapse. We hypothesized that FEV1decline, airway hyperresponsiveness (AHR), and quality of life (QOL) deteriorate after ICS cessation even after prolonged use.

Ambient particulate matter (PM) exposure is associated with children’s respiratory health. Little is known about the importance of different PM constituents. We investigated the effects of PM constituents on asthma, allergy, and lung function until the age of 11–12 years.

Chronic obstructive pulmonary disease is mainly a smoking-related disorder and affects millions of people worldwide, with a large effect on individual patients and society as a whole. Although the disease becomes clinically apparent around the age of 40–50 years, its origins can begin very early in life. Different risk factors in very early life—ie, in utero and during early childhood—drive the development of clinically apparent chronic obstructive pulmonary disease in later life. In discussions of which risk factors drive chronic obstructive pulmonary disease, it is important to realise that the disease is very heterogeneous and at present is largely diagnosed by lung function only. In this Review, we will discuss the evidence for risk factors for the various phenotypes of chronic obstructive pulmonary disease during different stages of life.

Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in children aged 4–8 years.

Background: Little is known about risk factors for the progression of disease in individuals with newly developed chronic bronchitis (CB). In addition to the effects of smoking, there was specific [...]

Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight.