Familial interstitial pneumonia links to pulmonary fibrosis risk in asymptomatic relatives
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Key takeaways:
- Annual incidence of asymptomatic pulmonary fibrosis in relatives of those with familial interstitial pneumonia was high.
- Patients with asymptomatic pulmonary fibrosis showed worsening dyspnea.
For individuals related to someone with familial interstitial pneumonia, the prevalence of pulmonary fibrosis was around 1,000 per 100,000 person-years, according to study results.
“Pulmonary fibrosis should be considered when anyone over 50 years of age presents with unexplained dyspnea, especially if that patient has a relative with pulmonary fibrosis,” David A. Schwartz, MD, distinguished professor of medicine and immunology and director of the Program to Advance Physician Scientists and Translational Research at University of Colorado’s Anschutz School of Medicine, told Healio.
In a prospective cohort study published in American Journal of Respiratory and Critical Care Medicine, Schwartz and colleagues analyzed 296 adults (median age, 58 years; 38% men) who were first-degree relatives of at least two people with familial interstitial pneumonia to determine the prevalence and development of preclinical (asymptomatic) pulmonary fibrosis in this patient population.
Individuals included in this analysis underwent two screenings, one at baseline and one 4 years after the first screening, that each involved a health questionnaire and a chest high-resolution CT (HRCT) scan.
Preclinical pulmonary fibrosis was found on 44 patients’ first HRCT scans, leaving 252 with normal scans as determined by pulmonologists involved in the study. Sixteen of these patients were later found to have pulmonary fibrosis in the follow-up evaluation, according to researchers.
Of 244 individuals not deemed to have preclinical pulmonary fibrosis at baseline by both blinded radiologists and pulmonologists, both parties agreed that in the median period of 3.9 years from first HRCT scan to second scan, 11 acquired the disease. Based on this finding, researchers estimated an annual incidence of preclinical pulmonary fibrosis of 1,023 per 100,000 person-years (95% CI, 511-1,831 per 100,000 person-years).
When evaluating worsening dyspnea based on initial scans, a greater proportion of patients with preclinical pulmonary fibrosis demonstrated this characteristic than those without the disease (38.4% vs. 15.4%; P = .002). Researchers also found a link between worsening dyspnea and usual interstitial pneumonia (P < .0002), as well as heightened quantitative fibrosis scores from initial screening (P < .001).
Out of 493 individuals who received a baseline screening (n = 296 with a follow-up; n = 197 without a follow-up), researchers reported that 18 died, and the deaths were evenly split among those with and without baseline preclinical pulmonary fibrosis. While progressive respiratory failure was behind six of the nine deaths in the group of patients with the disease at baseline, it did not cause any of the deaths in those without preclinical pulmonary fibrosis.
Poorer survival was found in those with preclinical pulmonary fibrosis detected on the first HRCT (P < .001) in Kaplan-Meier analysis, according to researchers. A couple demographic and clinical factors were linked to lower survival in univariate Cox proportional hazards; however, a multivariable Cox model adjusted for age and smoking showed a relationship between quantitative fibrosis score, determined by machine learning data-driven texture analysis, and poorer survival (P = .01).
“We were surprised by the extremely high incidence (new cases) of early pulmonary fibrosis that was 100-fold higher than that reported for sporadic idiopathic pulmonary fibrosis (IPF),” Schwartz told Healio. “We were also surprised by the high rate of progression and the associated decreased survival among those with early pulmonary fibrosis. In aggregate, this suggests that IPF is markedly under-diagnosed in the community and that early pulmonary fibrosis progresses rapidly.”
Additionally, researchers found higher frequency and odds for the minor allele of the gain-of-function MUC5B promoter variant rs35705950 in those with preclinical pulmonary fibrosis at baseline and follow-up vs. those without (OR = 1.5; 95% CI, 0.82-2.76).
“These findings suggest family history and the MUC5B promoter variant put individuals at higher risk of asymptomatic early pulmonary fibrosis,” Schwartz told Healio. “Given the poor outcome of these individuals and the likely benefit of earlier treatment, patients that have high risks for developing early, asymptomatic pulmonary fibrosis should consider screening with chest HRCT scans.”
This study by Schwartz and colleagues offers a significant contribution to support for screening for asymptomatic pulmonary fibrosis and emphasizes future studies centered on screening modalities, according to an accompanying editorial by Bridget F. Collins, MD, clinical associate professor in the division of pulmonary, critical care and sleep medicine at the University of Washington.
“Given the known high costs of IPF and progressive PF in symptoms, loss of life and health care spending, it seems prudent to determine how to best screen those known to be at highest risk,” Collins wrote. “A primary question arising from this study is optimal mode of screening, monitoring and time frame. Screening by family history is appealing, given its low cost, but would potentially miss disease in individuals for whom family history is unknown or where families are small. Up to 25% of patients with familial interstitial pneumonia may have mutations in telomere-related genes, making them more susceptible to the adverse effects of radiation, raising concerns about serial HRCT. Although quantitative CT with data-driven textural analysis may be particularly helpful in detecting subtle abnormalities that track with mortality, it is neither widely available nor standardized.”
For more information:
David A. Schwartz, MD, can be reached at david.schwartz@cuanschutz.edu.