Combined Pulmonary Fibrosis Emphysema: Role of Cigarette Smoking and Pulmonary Hypertension in a Rural Cohort

Abstract

Background Disease heterogeneity in idiopathic pulmonary fibrosis (IPF) often complicates the systematic study of disease, management of patients and clinical investigations. Objective To describe combined pulmonary fibrosis emphysema (CPFE) phenotype in a rural Appalachian IPF cohort with the highest smoking rates in the United States. Methods CPFE patients (n = 60) in a developed IPF cohort (n = 153) were characterized. Groups (CPFE vs IPF without emphysema) were categorized based on the predominant HRCT patterns of UIP (n = 109). Demographics, clinical variables, and treatment details were recorded. Kaplan–Meier survival and multivariate logistic regression analysis were performed. Results The prevalence of CPFE in our IPF cohort was 45% (n = 49). The CPFE group was younger (73.9 vs 78.2), had a more extensive smoking history (93.9% vs 53.3%) with greater mean smoking pack years (49.09 vs 15.39) and had lower percentage predicted DL CO on presentation (38.35 vs 51.09) compared to IPF without emphysema group. Both groups shared equivalent higher burden of comorbidities, including pulmonary hypertension (PH) (46.9% vs 33.3%). One-fifth of patients were prescribed antifibrotics and only a subset (5%) of patients underwent lung transplantation. There was a non-significant trend towards reduced survival in CPFE (p = 0.076). Smoking status and DL CO predicted CPFE in our cohort. Body mass index (BMI), PH, and pirfenidone use were significant predictors of mortality. Conclusion CPFE was highly prevalent in our rural IPF cohort. In contrast to previous studies, CPFE group was older and had higher female (approx. 30%) occurrence. A greater exposure to cigarette smoke and reduced DL CO at diagnosis predicted CPFE. Lower BMI and PH predicted higher mortality whereas use of pirfenidone improved survival in our cohort. This study highlights a complex interaction of cigarette smoking, advanced fibrosis of UIP, PH and potential utility of antifibrotic agents in CPFE phenotype. Substantial burden of comorbidities, older age, and the limited utilization of advanced therapeutics in the cohort emphasize the challenges faced by rural Appalachian patients.

Interstitial lung abnormalities and interstitial lung diseases associated with cigarette smoking in a rural cohort undergoing surgical resection

“…Moderate to severely reduced DL CO is a consistent and characteristic finding mentioned in CPFE patients reflecting the additive effects of emphysema and fibrosis on the reduction in surface area available for gas exchange [ 46 ]. A greater exposure to cigarette smoke and reduced DL CO were predictors for CPFE in a cohort of IPF patients [ 16 ]. Similar deleterious effect of emphysema in patients with interstitial features were reported by Ash SY et al based on limited availability of DL CO findings in their study participants (< 5%) [ 10 ].…”

“…The Appalachian region is challenged with the highest rates of smoking (25.2%) in the United States [ 14 ]. Subsequently, there is an excessive burden of lung disease associated with smoking in this region [ 15 , 16 ]. Employing a cohort diagnosed with lung nodule/mass and undergoing surgical resection, we (1) define the prevalence of ILAs/ILDs, (2) delineate clinical, radiographic and pathologic predictors of ILAs/ILDs, and (3) determine their associations with mortality.…”

Cigarette Smoke Exposure Increases Glucose-6-phosphate Dehydrogenase, Autophagy, Fibrosis, and Senescence in Kidney Cells In Vitro and In Vivo

“…CSE is a risk factor for the development of lung fibrosis [ 65 ]. Renal fibrosis is involved in various kidney diseases [ 66 ].…”

An increased risk of pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema: a meta-analysis

“…10,31,32 Some studies found that patients with CPFE had higher RVSP, or more large pulmonary trunk size, which were hemodynamic and radiological signs of PH, respectively. [33][34][35] Additionally, in our meta-analysis, different cutoffs of esPAP to diagnose PH were used in the selected studies. Thus, a subgroup analysis was conducted, and the results demonstrated the highest risk of PH with esPAP thresholds ≥ 50 mm Hg, a higher risk with a cutoff between 40 and 50 mm Hg, and a non-signi cantly high risk with a cutoff between 30 and 40 mm Hg in patients with CPFE compared with patients with IPF alone.…”