Constrictive (Obliterative) Bronchiolitis as Presenting Manifestation of Connective Tissue Diseases

Antonella Arcadu, MD; Jay H. Ryu, MD


J Clin Rheumatol. 2020;26(5):176-180. 

In This Article


To the best of our knowledge, this is the first study conducted in an attempt to determine whether CB can be the initial manifestation of an undiagnosed CTD. Among 44 patients diagnosed to have CB, 43% manifested positive autoimmune serologic results among whom more than one-third were diagnosed to have a CTD at presentation or during the following 2 years. Our results may underestimate the true prevalence of CTD in those patients presenting with CB because our follow-up data were incomplete, and the extent of evaluation, including rheumatology consultation, for the detection of underlying CTD varied among our study subjects. Rheumatoid arthritis and Sjogren syndrome were most frequently identified CTDs in these patients. This is consistent with what has been described in the literature regarding the prevalence of bronchiolar disorders, particularly CB, among patients with various CTDs.[11–13] Thus, in patients presenting with CB of unclear origin, the search for underlying CTD could be focused on these 2 CTDs, rheumatoid arthritis and Sjogren syndrome.

Only 9% of our patients had been correctly diagnosed to have CB, a poorly recognized form of obstructive lung disease, prior to pulmonary evaluation at our medical center. In patients with suspected or confirmed CTD, especially rheumatoid arthritis and Sjogren syndrome, evidence of airflow obstruction seen on PFT should raise the suspicion of CB. Subsequent evaluation should include HRCT with inspiratory and expiratory views.

Several studies evaluating the pathogenesis of CB have reported potential etiologic roles of viral respiratory infection, chronic gastroesophageal reflux, inhalation injuries, and exposure to certain drugs.[1,14–16] Furthermore, immune mechanisms have been described in patients with bronchiolitis obliterans syndrome in the context of solid organ or hematopoietic stem cell transplantation and in patients with paraneoplastic autoimmune multiorgan syndrome in whom airway biopsy has demonstrated the presence of the putative paraneoplastic autoantibodies.[1,16–18] The presence of positive autoimmune serology in nearly one-half of our patients initially diagnosed to have CB highlights the importance of considering autoimmune mechanisms and evaluation for CTDs in such patients, most of whom are female and nonsmokers.

The majority of our patients with CB were diagnosed on the basis of characteristic clinical and radiologic findings. In particular, the presence of mosaic attenuation pattern demonstrated on HRCT with evidence of air trapping on expiratory views in the absence of inconsistent findings (e.g., diffuse ground-glass nodules, patchy ground-glass opacities) is generally sufficient to diagnose CB.[2,19] In our study, 15 patients (34%) underwent lung biopsies and included 5 surgical lung biopsies. Previous studies demonstrated that the histological abnormalities can have a patchy distribution, even in presence of more severe disease, and specimens can be false-negative if sampled inadequately.[2,20] Although all 5 surgical lung biopsies demonstrated histopathologic evidence of CB, only one of bronchoscopic lung biopsies was diagnostic.

Treatment of CB in our patients included macrolides, inhaled corticosteroids or bronchodilators, oral corticosteroids, and various steroid-sparing agents. Optimal treatment of CB, whether CTD-related or cryptogenic, remains unclear because the existing data consist mostly of case reports and small case series.[21–24] Long-term treatment with macrolide antibiotics has been used for their immunomodulatory properties in patients with CB of diverse etiologies including solid organ or hematopoietic stem cell recipients with bronchiolitis obliterans syndrome.[25–27] Unfortunately, the small number of subjects in our study and the incomplete follow-up did not allow adequate assessment of therapeutic efficacy associated with these medications in this setting.

Our study has several limitations. First, this was a study of available medical records, and the follow-up data were incomplete including those related to pulmonary function measurements. The number of study subjects was modest because CB is an uncommon disorder and commonly misdiagnosed as asthma or chronic obstructive pulmonary disease. The extent of diagnostic evaluation in regard to possible CTD varied according to individual clinicians assessing the study subjects. For example, although all 7 patients diagnosed to have CTD and 6 other patients with positive CTD serology underwent a rheumatologic consultation, the remaining 31 patients did not. In addition, the majority of our patients did not undergo lung biopsy. To our knowledge, however, this is the first study to address the issue of CB as the initial manifestation of CTD.

In conclusion, our study demonstrated that nearly one-half of patients with cryptogenic CB manifest positive CTD serology, and some of these patients subsequently develop clinical evidence of a CTD not previously diagnosed. These results demonstrate that CB can be the presenting manifestation of an underlying CTD. The main predictor for CTD in patients with CB is the presence of a positive autoimmune serology.