Interactions between Cigarette Smoking and the Natural History of Idiopathic Pulmonary Fibrosis

doi:10.1378/chest.98.1.71

Chest

Volume 98, Issue 1, July 1990, Pages 71-76

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Idiopathic pulmonary fibrosis is characterized by an inflammation of the walls of the respiratory airspaces that proceed to fibrotic alveolar derangement. Smoking habits are associated with changes in the number and the activation state of immune and inflammatory alveolar cells. Cigarette smoke could interact with the course of this disease. To evaluate the effects of smoking on IPF, 11 smokers and 16 nonsmokers were compared. Clinical presentation, PFTs, BAL cell populations, short-term glucocorticoid responsiveness and survival were evaluated. Similar PFT results were observed in both groups. Lymphocyte cells were higher in nonsmokers than in smokers. Glucocorticoid responsiveness was mainly observed in nonsmokers. Nonsmoking status was not associated with survival advantage. We conclude that the subset of IPF characterized by an aggressive onset, a BAL fluid high lymphocyte count and a substantial PFT improvement after therapy began, occurs predominantly in the absence of cigarette smoking habits.

Section snippets

Patients

The study population consisted only of consecutive new patients with IPF observed between May 1977 and May 1987. Three patients who quit smoking between the onset of dyspnea and the BAL procedure were excluded from this study, in view of such an ambiguous past smoking history. In all cases no patients had known causes of pulmonary fibrosis, such as organic or inorganic dust inhalation, drug ingestion or primary granulomatous lung disorders. No patients had received glucocorticoids or any other

Cigarette Smoking in the Study Population

As shown in Table 1,11 patients (40.7 percent) were smokers. Among this group, the mean consumption at the time of the BAL procedure was 22.5 ± 3.3 cigarettes/day (range: 12 to 40 cigarettes/day). Sixteen patients were nonsmokers, two of them had given up smoking habits 5 and 16 years before dyspnea onset, others were life-long nonsmokers. The male/female ratio was higher in smokers (9:2) than in nonsmokers (5:11; p<0.01).

Cigarette Smoking, Pulmonary Function and IPF Onset

In nonsmokers the exertional dyspnea as expressed by the mean dyspnea

Discussion

Different findings emerge from the present study dealing with the interactions between cigarette smoking and the course of IPF. First, despite similar PFT results, nonsmokers had a shorter duration of symptoms at the time of presentation than smokers. Second, nonsmokers had higher alveolar lymphocyte counts than smokers. Third, the prednisolone therapy was more efficient in nonsmokers than in smokers. Finally, when males and females were compared, with re3spect to smoking habits, we did not

Cigarette Smoking Habit in IPF

In most of the reports concerning IPF, higher rates of smokers or exsmokers (60 to 80 percent) are observed than in the present study (40.7 percent).²,14, 15, 16, 17, 18, 19, 20 This discrepancy may be related to different study populations and the exclusion of patients who had given up smoking habits between clinical onset and BAL procedure, but whatever its origin, this lower rate of smoking habits may explain in some way why we had the opportunity to compare two contrasted groups of patients.

Cigarette Smoking and Onset of IPF

The observation of shorter dyspnea duration at the time of presentation in the absence of smoking habits could reflect either true differences in disease duration or the unreliability of the clinical appraisal of such a subjective parameter. Indeed, it could reflect a recall bias affecting smokers and nonsmokers differently, ie, dyspnea could disturb earlier nonsmokers than smokers leading, in the absence of smoking habits, to early medical advice and prompt IPF recognition. Moreover the longer

Cigarette Smoking and BAL Cell Populations

In the present series, a higher number of lymphocytes was observed in BAL fluids from nonsmokers than from smokers. Previous studies have reported a clear relationship between high lymphocyte counts in BAL fluid with clinical or pathologic evidence of IPF activity.¹⁶,²⁰,²⁴ In the pathogenesis of IPF, autoimmune reactions against the alveolar wall components are hypothesized to be the eliciting event leading to interstitial inflammation involving lymphocytes,²⁵ mostly of the T subset.²⁶ An

Cigarette Smoking, and Prednisolone Response

After prednisolone therapy, there was a striking contrast between nonsmokers who fairly often showed a high lymphocyte count in BAL with a substantial prednisolone response and smokers with nearly normal lymphocyte count and no PFT improvement. The observation of such a relationship between lymphocyte count in BAL and prednisolone responsiveness already has been reported.¹⁶,²⁰,²⁴ Similarly, a subacute onset with low PFT results despite dyspnea of short duration has been shown to be associated

Smoking Habits and Survival

Despite the initial corticosteroid efficiency in nonsmokers, the overall prognosis of IPF as assessed by survival time was similar in nonsmokers and in smokers as already shown by Turner-Warwick and coworkers. ¹⁴

Male-Female Differences

Our population study confirms that there are some male-female differences in the course of IPF. However, our data argue against the hypothesis that this gender difference accounts, per se, for such a discrepancy and suggests that it is mainly related to differences in smoking habits. So the better results of treatment previously observed among women¹⁷^,²⁰ should be reevaluated taking into account the detailed smoking history of the patients.

In conclusion, the clinical variant of IPF

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2000, Clinics in Chest Medicine
Citation Excerpt :
An early study found similar BAL cell counts in smokers versus nonsmokers with IPF,65 but two more recent studies have revealed significant differences between the two populations. De Cremoux and associates38 found that smokers with IPF had significantly more macrophages and fewer lymphocytes than nonsmokers with the disease. Schwartz and colleagues128 compared patients with IPF to both nonsmoking and smoking volunteers.
Cigarette smoking is the leading cause of preventable death in the United States.² Smoking adversely affects many organ systems, but especially the lung. Carcinoma of the lung and chronic obstructive pulmonary disease account for most smoking-associated morbidity and mortality, and their association with smoking is both well established and widely recognized.² In addition, smoking has a substantial and increasingly recognized adverse impact on the respiratory health of children.⁴²
Cigarette smoking also is associated with differences in the incidence, severity, or natural history of a broad array of other respiratory illnesses, ranging from the common cold to pneumothorax, pulmonary hemorrhage, and various interstitial lung diseases (Box 1).
Interestingly, whereas the general effect of smoking on respiratory diseases is adverse, in the cases of sarcoidosis and hypersensitivity pneumonitis, smoking may actually be associated with a decrease in the incidence of disease. The strength of the association between smoking and specific diseases varies considerably, and there are limitations in the methods used to establish association and to control for potentially confounding factors such as socioeconomic status.
The mechanisms by which smoking affects the incidence or severity of various lung diseases are not entirely clear. In this review, the authors briefly discuss some of the pulmonary and systemic effects of smoking that might mediate its effects on an array of lung diseases, then comprehensively review less common or less well-recognized smokingaffected lung diseases such as pulmonary infections, spontaneous pneumothorax, Goodpasture's syndrome, eosinophilic granuloma and other interstitial lung diseases, and pulmonary metastatic disease.
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To determine the median survival of patients with cryptogenic fibrosing alveolitis, in comparison to that expected of individuals of the same age and sex from the general population. To estimate the effect of survival bias incurred by studying both incident and prevalent cases. To identify factors associated with survival.
Cohort study.
Nine hospitals from the Trent Region of England.
Two hundred forty-four cases of cryptogenic fibrosing alveolitis: 168 patients were alive on day 1 of the study (prevalent cases), and 76 patients had newly diagnosed conditions over a prospective 18-month period of patient recruitment (incident cases).
Age, sex, date of diagnosis, lung function at presentation, and details of treatment prescribed were extracted from hospital clinical records. Data on lifetime smoking habits were collected by postal questionnaire. Vital status was established from the general practitioner. The expected survival of each case was extracted from the English life tables.
Median survival for incident cases was 2.9 years and for prevalent cases 9 years, compared to expected values of 10 and 13 years, respectively. Incident cases had significantly worse survival than prevalent cases, even after adjustment for the effects of age, sex, smoking history, lung function at presentation, and treatment (hazard ratio, 4.53 [95% confidence interval, 2.71 to 7.56]; p<0.001). Lower FVC at presentation and the use of corticosteroid treatment were both associated with worse survival.
The inclusion of prevalent cases leads to significant overestimation of the median survival for patients with cryptogenic fibrosing alveolitis. In newly diagnosed cases of cryptogenic fibrosing alveolitis, median survival is only 2.9 years, and expected life span is reduced by approximately 7 years.
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Results: Persons living in households that primarily use biomass for cooking fuel have substantially higher prevalence of active tuberculosis than persons living in households that use cleaner fuels (odds ratio [OR] = 3.56; 95% confidence interval [Cl] = 2.82−4.50). This effect is reduced somewhat when availability of a separate kitchen, house type, indoor crowding, age, gender, urban or rural residence, education, religion, caste or tribe, and geographic region are statistically controlled (OR = 2.58; 95% Cl = 1.98−3.37). Fuel type also has a large effect when the analysis is done separately for men (OR = 2.46; 95% Cl = 1.79−3.39) and women (OR = 2.74; 95% Cl = 1.86−4.05) and separately for urban areas (OR = 2.29; 95% Cl = 1.61−3.23) and rural areas (OR = 2.65; 95% Cl = 1.74−4.03). The analysis also indicates that, among persons age 20 years and over, 51% of the prevalence of active tuberculosis is attributable to cooking smoke.
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: Manuscript received July 31; revision accepted December 1.

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Chest

Introducing New Members of the Editorial Board Clinical InvestigationInteractions between Cigarette Smoking and the Natural History of Idiopathic Pulmonary Fibrosis

Section snippets

Patients

Cigarette Smoking in the Study Population

Cigarette Smoking, Pulmonary Function and IPF Onset

Discussion

Cigarette Smoking Habit in IPF

Cigarette Smoking and Onset of IPF

Cigarette Smoking and BAL Cell Populations

Cigarette Smoking, and Prednisolone Response

Smoking Habits and Survival

Male-Female Differences

Chest

Eosinophilic granuloma of lung: clinical aspects of primary pulmonary histiocytosis in the adult

Medicine

Natural history and treated course of usual and desquamative interstitial pneumonia

N Engl J Med

Cigarette smoke, asbestos, and small irregular opacities

Am Rev Respir Dis

Effects of cigarette smoking on dogs

Arch Environ Health

Corporate author. A national survey of bird fanciers’ lung: including its possible association with jejunal villous atrophy

Br J Dis Chest

Epidemiological study of farmers lung in five districts of the French Doubs province

Thorax

Precipiting antibodies of farmer's lung antigens in a Wisconsin farming population

Am Rev Respir Dis

Factors influencing the development of serum precipitins to farmer's lung antigen in Quebec dairy farmers

Thorax

Smoking and pulmonary sarcoidosis: effects of cigarette smoking on prevalence clinical manifestations, alveolitis and evolution of the disease

Thorax

The effect of cigarette smoke on bleomycin-induced pulmonary fibrosis in hamsters

Am Rev Respir Dis

Oxidants spontaneously released by alveolar macrophages of cigarette smokers can inactive the active site of al antitrypsine, rendering it ineffective as an inhibitor of neutrophil elastase

J Clin Invest

Increase cathepsin B like in alveolar macrophages and bronchoalveolar lavage fluid from smokers

Am Rev Respir Dis

Cryptogenic fibrosing alveolitis: clinical features and their influence on survival

Thorax

Cryptogenic fibrosing alveolitis: response to corticosteroid treatment and its effect on survival

Thorax

Cryptogenic fibrosing alveolitis: relationships of pulmonary physiology and bronchoalveolar lavage to response to treatment and prognosis

Am Rev Respir Dis

The prognosis of cryptogenic fibrosing alveolitis

Thorax

Introducing New Members of the Editorial Board Clinical Investigation
Interactions between Cigarette Smoking and the Natural History of Idiopathic Pulmonary Fibrosis