Cryptogenic fibrosing alveolitis and lung cancer: the BTS study

Our plain-English summary of Cryptogenic fibrosing alveolitis and lung cancer: the BTS study, by J.M. Harris, I.D. Johnston, R. Rudd, et al (Thorax, 2010).

The study

• Authors: J.M. Harris, I.D. Johnston, R. Rudd, A.J. Taylor, P. Cullinan
• Journal: Thorax
• Published: 2010;65(1):70-6
• Cited by: 72 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA).

Methods: Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated.

Results: 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02).

Conclusions: These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

In plain English

This study followed 588 patients with cryptogenic fibrosing alveolitis (CFA), a scarring lung disease. They were entered by chest physicians across England, Scotland and Wales from December 1990. The authors traced deaths to 31 December 2001 and compared lung cancer deaths with numbers expected from national rates adjusted for age, sex and calendar period. By then 488 patients had died, 46 of them from lung cancer. That was 7.40 times the expected number (95% CI 5.42 to 9.88). Excluding people who died within 5 years of presentation, the ratio fell to 1.79 (95% CI 0.72 to 3.69). Six physicians graded the asbestos exposure patients reported on a questionnaire. The 25 judged to have at least moderate exposure had 13.1 times the expected lung cancer deaths (95% CI 3.6 to 33.6); the rest had 7.2 times (95% CI 5.2 to 9.7). The authors noted that these confidence intervals overlapped. All but two lung cancer deaths were in smokers. The authors concluded that CFA is associated with lung cancer but the link may not be causal, and that smoking could be confounding it.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cohort mortality study: a prospectively recruited UK cohort of patients with CFA, traced through death records. Observed lung cancer deaths were compared with deaths expected from national rates adjusted for age, sex and calendar period (standardised mortality ratios, SMRs).
• Who was studied: 588 patients with a definite diagnosis of CFA (clinical or histological criteria). They were entered by 150 chest physicians in England, Scotland and Wales during a 2-year enrolment starting 1 December 1990, and vital status was followed to 31 December 2001. People with occupational exposures accepted as enough for a pneumoconiosis compensation diagnosis were excluded.
• Exposure: Self-reported exposure to asbestos and other dusts, collected by questionnaire at enrolment. 87 patients (15.0%) reported possible asbestos exposure. Six consultant respiratory physicians graded each subject's exposure as none, mild, moderate or heavy, and 25 were classed as at least moderate. Duration of 10 years or more was also analysed. Smoking history was recorded. The article does not name fiber types.
• Main results:
  • Of the cohort, 488 had died by 31 December 2001, and 46 of these deaths (9.4%) were from lung cancer.
  • Across the whole cohort, lung cancer deaths were 7.40 times the number expected from national rates (95% CI 5.42 to 9.88).
  • When people who died within 5 years of presentation were excluded, the excess fell to 1.79 (95% CI 0.72 to 3.69).
  • Compared with national rates, patients graded as having at least moderate asbestos exposure (n = 25) had an SMR of 13.1 (95% CI 3.6 to 33.6). Patients with less or no asbestos exposure had an SMR of 7.2 (95% CI 5.2 to 9.7). Both are observed-to-expected ratios, not a direct comparison between the two groups.
  • Patients reporting any asbestos exposure (n = 87) had an SMR of 10.65 (95% CI 5.32 to 19.06), compared with 6.76 (95% CI 4.71 to 9.40) for those with no reported exposure.
  • Patients reporting at least 10 years of asbestos exposure (n = 38) had an SMR of 18.58 (95% CI 8.03 to 36.66).
  • The authors stated that the asbestos estimates were wide and their confidence intervals overlapped. The estimates also tended toward no excess when people who died soon after presentation were excluded.
  • Of the 46 lung cancer deaths, only two (4.3%) were in never smokers and only six (13.0%) were in women.
  • Current smokers had an SMR of 14.67 (95% CI 8.83 to 22.92). The national comparison rates could not be adjusted for smoking.
  • For cancers other than lung cancer, the SMR was 1.41 (95% CI 0.90 to 2.09), which the authors said was not statistically significant.
• The authors' conclusion: The authors concluded that the findings confirm an association between CFA and lung cancer, but that the relationship may not be causal. They suggested that smoking could be confounding the association.
• Limitations the authors state:
  • Smoking was very common in the cohort and could be confounding the association, since national rates could not be adjusted for smoking.
  • Some of the excess lung cancer deaths may reflect asbestosis that was misclassified as CFA.
  • The order of events is uncertain: many lung cancers were probably already present when patients were first seen, and the risk estimates fell rather than rose with longer survival.
  • Ascertainment bias (Berkson's bias) is possible: lung cancer may have been picked up more often among smokers or among people who already had lung cancer.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Asbestos Exposure, Confounding.

Related studies

• British Thoracic Society study of cryptogenic fibrosing alveolitis: current presentation and initial management. Fibrosing Alveolitis Subcommittee of the Research Committee of the British Thoracic Society — I.D. Johnston, R.J. Prescott, et al. (1997)
• Fine structural changes in cryptogenic fibrosing alveolitis and asbestosis — B. Corrin, A. Dewar, et al. (1985)
• Desquamative interstitial pneumonitis. Cellular phase of fibrosing alveolitis — R.R. Tubbs, S.P. Benjamin, et al. (1977)
• Cryptogenic Fibrosing Pleuritis — A. Manco, V. Alfieri, et al. (2021)
• What role for asbestos in idiopathic pulmonary fibrosis? Findings from the IPF job exposures case-control study — C.J. Reynolds, R. Sisodia, et al. (2023)
• Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis — K.A. Khan, M.P. Kennedy, et al. (2015)

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