Bronchoalveolar Lavage and Response to Cyclophosphamide in Scleroderma Interstitial Lung Disease

Abstract

Rationale: The presence of inflammatory cells on bronchoalveolar lavage is often used to predict disease activity and the need for therapy in systemic sclerosis-associated interstitial lung disease. Objectives: To evaluate whether lavage cellularity identifies distinct subsets of disease and/or predicts cyclophosphamide responsiveness. Methods: Patients underwent baseline lavage and/or high-resolution computed tomography as part of a randomized placebo-controlled trial of cyclophosphamide versus placebo (Scleroderma Lung Study) to determine the effect of therapy on forced vital capacity. Patients with 3% or greater polymorphonuclear and/or 2% or greater eosinophilic leukocytes on lavage and/or ground-glass opacification on computed tomography were eligible for enrollment. Measurements and Main Results: Lavage was performed in 201 individuals, including 141 of the 158 randomized patients. Abnormal cellularity was present in 101 of these cases (71.6%) and defined a population with a higher percentage of men (P 5 0.04), more severe lung function, including a worse forced vital capacity (P 5 0.003), worse total lung capacity (P 5 0.005) and diffusing capacity of the lung for carbon monoxide (P 5 0.004), more extensive ground-glass opacity (P 5 0.005), and more extensive fibrosis in the right middle lobe (P 5 0.005). Despite these relationships, the presence or absence of an abnormal cell differential was not an independent predictor of disease progression or response to cyclophosphamide at 1 year (P 5 not significant). Conclusions: The presence of an abnormal lavage in the Scleroderma Lung Study defined patients with more advanced interstitial lung disease but added no additional value to physiologic and computed tomography findings as a predictor of progression or treatment response. Clinical trial registered with www.clinicaltrials.gov (NCT 000004563).

Correlation of Cough With Disease Activity and Treatment With Cyclophosphamide in Scleroderma Interstitial Lung Disease

“…Lavage of the right middle lobe alone may have underestimated the cellularity of the lung, affecting the correlation with cough. 21,27 The retention of patients for follow-up questionnaires also limits the power of the study, because 20% of patients did not complete the follow-up. The low number of patients describing cough as severe or very frequent may also limit the power for assessing improvement in cough severity.…”

“…20 BAL BAL was performed in the right middle lobe or lingula prior to randomization in each center using standardized methods as described previously. 21 The stained slides were interpreted by readers at the individual sites and confi rmed at the core facility at the Medical University of South Carolina. There were no reports of other tracheobronchial conditions such as neoplasm or xerotrachea, which could have been responsible for cough symptoms.…”

Interstitial Lung Disease in Systemic Sclerosis: Diagnosis and Management

“…Early studies correlated increased granulocytes in BAL with increased response to immunosuppression presumably because this represented active alveolitis [34,35]. Subsequently, BAL granulocytosis has been shown to correlate with the degree of ground glass opacity seen on HRCT [30] and with more advanced interstitial disease [36]. However, data from the Scleroderma Lung Study suggest that BAL granulocytosis does not add any additional prognostic information to HRCT and pulmonary function measures and is not a predictor of treatment response [36,37].…”

“…Subsequently, BAL granulocytosis has been shown to correlate with the degree of ground glass opacity seen on HRCT [30] and with more advanced interstitial disease [36]. However, data from the Scleroderma Lung Study suggest that BAL granulocytosis does not add any additional prognostic information to HRCT and pulmonary function measures and is not a predictor of treatment response [36,37]. There is no question that BAL is an important test in the consideration of infection.…”

Inhibition of Thrombin as a Novel Strategy in the Treatment of Scleroderma-Associated Interstitial Lung Disease

“…Characterized by microvascular injury and inflammation, SSc-ILD culminates in excessive deposition of extracellular matrix proteins, often resulting in severe lung dysfunction and death. Although cyclophosphamide treatment may stabilize lung function in some patients, longterm treatment is required and significant toxicity may occur (Berezne et al, 2007; Strange et al, 2008). There is, therefore, a great need for new therapeutic approaches that would be more effective and less toxic than current treatments.…”