Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences.

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (DlCO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and DlCO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in DlCO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.

Idiopathic Pulmonary Fibrosis and Lung Cancer. A Systematic Review and Meta-analysis.

Rationale: The association between idiopathic pulmonary fibrosis (IPF) and lung cancer has been previously reported. However, there is the potential for significant confounding by age and smoking, and an accurate summary risk estimate has not been previously ascertained.Objectives: To determine the risk and burden of lung cancer in patients with IPF, accounting for known confounders.Methods: We conducted a comprehensive literature search of MEDLINE, EMBASE, and SCOPUS databases and used the Newcastle Ottawa criteria to assess study quality. We then assessed the quality of ascertainment of IPF cases based on modern consensus criteria. Data that relied on administrative claims or autopsies were excluded. We calculated summary risk estimates using a random effects model.Results: Twenty-five cohort studies were included in the final analysis. The estimated adjusted incidence rate ratio from two studies was 6.42 (95% confidence interval [CI], 3.21-9.62) and accounted for age, sex, and smoking. The summary incidence rate from 11 studies was 2.07 per 100 person-years (95% CI, 1.46-2.67), and the summary mortality rate was 1.06 per 100 person-years (95% CI, 0.62-1.51) obtained from three studies. The summary prevalence from 11 studies was 13.74% (95% CI, 10.17-17.30), and the proportion of deaths attributable to lung cancer was 10.20 (95% CI, 8.52-11.87) and was obtained from nine studies.Conclusions: IPF is an increased independent risk factor for lung cancer, even after accounting for smoking. Further well-designed studies using modern consensus criteria are needed to explore mechanisms of this association.

The effect of radiographic emphysema in assessing lung cancer risk.

PURPOSE: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial. METHODS: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema. RESULTS: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2). CONCLUSION: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients.

The Relationship Between Tobacco Smoke Exposure and Airflow Obstruction in US Children: Analysis of the National Health and Nutrition Examination Survey (2007-2012).

BACKGROUND: It has been difficult to determine the individual impact of prenatal and postnatal tobacco smoke exposure (TSE) on childhood lung function, as children are often exposed to both. OBJECTIVE: The goal of this study was to determine the association between current TSE and airflow obstruction while adjusting for self-reported prenatal TSE. METHODS: Children aged 6 to 11 years who participated in the National Health and Nutrition Examination Survey (2007-2012) who had serum cotinine levels measured and spirometry performed were included. Logistic regression was used to determine the association between log-transformed serum cotinine level and airflow obstruction while adjusting for confounders; the analysis was then stratified according to asthma status. The final model included both log-transformed serum cotinine level and prenatal exposure as covariates. RESULTS: The sample consisted of 2,070 children; 9.6% had airflow obstruction. The association between cotinine levels and airflow obstruction was significant in an unadjusted analysis (OR, 1.12 [95% CI, 1.02-1.23]). In the multivariate analysis with both exposures included as covariates, serum cotinine level was not significantly associated with airflow obstruction (ORadj, 1.07 [95% CI, 0.94-1.21]), and no association was seen in children with asthma and nonasthmatic children. Prenatal smoking was associated with airflow obstruction in children with asthma (ORadj, 2.51 [95% CI, 1.08-5.79]) but not in nonasthmatic children (ORadj, 1.08 [95% CI, 0.53-2.18]). CONCLUSIONS: Current TSE was not independently associated with airflow obstruction in school-aged children. Prenatal TSE was associated with airflow obstruction in children with asthma. Repeated studies into potential mediators and confounders of this relationship are needed.