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


Clinical, Pulmonary Function, and Radiologic Features at Presentation

Demographic, clinical, and pulmonary function data at presentation are summarized in Table 1. The mean age at initial presentation was 60.5 (SD, 13.8) years; 38 (86%) were women, and 32 (73%) were never smokers. Presenting symptoms included shortness of breath in all patients with cough noted in nearly two-thirds. The onset of respiratory symptoms preceded the diagnosis of CB by a median interval of 2 years (range, 0.1–35 years). Auscultation of the lungs did not reveal adventitious sounds in the majority of patients; inspiratory crackles were noted in 10 patients (23%) and wheezing in 4 patients (9%).

The referral diagnoses at the time of initial pulmonary evaluation at our medical center are outlined in Table 2. The most common was persistent exertional dyspnea of undetermined cause. Twelve patients (27%) had been diagnosed to have chronic obstructive pulmonary disease, emphysema, or asthma. Only 4 patients (9%) were referred with the correct diagnosis of CB (obliterative bronchiolitis, bronchiolitis obliterans).

An obstructive pattern on PFT was found in 38 patients (86%). A mixed pattern of obstructive and restrictive abnormalities was seen in 2 patients (5%). A nonspecific pattern of abnormalities (reduced FEV1 and forced vital capacity with a normal FEV1/forced vital capacity ratio) was found in 2 patients (5%). One patient (2%) had normal pulmonary function results, and 1 remaining patient (2%) exhibited a restrictive pattern; there was no evidence of interstitial lung disease or other findings to explain the restrictive pattern except for prior sternotomy for aortic valve surgery.

Chest radiographs were available for review in 35 patients (80%) and demonstrated normal findings (n = 21 [60%]) or hyperinflation (n = 8 [23%]) without parenchymal opacities in most patients; mild scattered reticular opacities were noted in a minority (n = 6 [17%]). All 44 patients had HRCT available for review and demonstrated mosaic attenuation pattern in all patients, air trapping was demonstrable on expiratory images in 43 (98%); in the remaining patient, the diagnosis of CB was confirmed on surgical lung biopsy that was performed for evaluation of persistent dyspnea and airflow obstruction.

Lung Biopsy Data

Transbronchial biopsies were performed in 10 patients (23%) and yielded evidence of CB in only 1 patient (10%). Surgical lung biopsy was performed in 5 patients (11%) and confirmed the diagnosis of CB in all 5 patients.

Autoimmune Serologic Results and CTDs

All 44 patients underwent serologic screening for autoimmune diseases, which was positive in 19 patients (43%) (Table 3). The extent of serologic testing was determined by individual clinicians. Most frequently positive tests included antinuclear antibodies, anti-CCP antibody, and rheumatoid factor.

Three patients (7%) were diagnosed to have an underlying CTD at the time of their initial evaluation for CB at our medical center. These diagnoses included rheumatoid arthritis, Sjogren syndrome, and undifferentiated CTD, respectively; all 3 patients had positive autoimmune serology results. Clinical follow-up (median duration, 41 months; range, 2–384 months) was available in 30 of the remaining 41 patients, and 4 additional patients (13%) were diagnosed to have a CTD after a median interval of 2 months (range, 1–15 months). The diagnoses in these 4 patients included rheumatoid arthritis (3 patients) and Sjogren syndrome (1 patient). All 4 patients manifested positive autoimmune serologic results at the time of their initial pulmonary evaluation at our medical center. For all 7 patients diagnosed to have CTD, the onset of respiratory symptoms preceded the CTD diagnosis by a median interval of 24 months (range, 6–36 months). These 7 CTD patients comprised 38% of 19 patients CB who manifested positive autoimmune serologic results at baseline evaluation.

Treatment and Outcomes

Forty-three patients (98%) received pharmacologic therapy for the treatment of CB or underlying CTD. Oral corticosteroids were administered to 28 patients (64%). Fourteen patients (32%), including all 7 patients with CTD, received steroid-sparing agents, including mycophenolate (6 patients), hydroxychloroquine (3 patients), methotrexate (2 patients), etanercept (2 patients), and azathioprine (2 patients). Inhaled corticosteroids and inhaled bronchodilators were administered in 33 (75%) and 35 patients (80%), respectively. Twenty-three subjects (52%) received a long-term macrolide treatment with azithromycin (n = 20 [45%]) or clarithromycin (n = 3 [6%]). Supplementary oxygen therapy was prescribed for 11 patients (25%) at the time of CB diagnosis.

Follow-up PFT data were available in 24 patients (55%) including 6 of 7 patients with CTD. There was evidence of improvement in airflow obstruction (increase of FEV1 >20% above baseline) in only 2 patients (8%); 1 patient had rheumatoid arthritis (treated with prednisone, mycophenolate mofetil, inhaled corticosteroids, and azithromycin), and the other patient had Sjogren syndrome (treated with prednisone, hydroxychloroquine, mycophenolate mofetil, inhaled corticosteroids, and azithromycin). Evidence of worsening (decrease of FEV1 >20% below baseline) was seen in 7 patients (29%) including 2 patients with rheumatoid arthritis (1 patient treated with prednisone, leflunomide, mycophenolate mofetil, and inhaled corticosteroids; another patient treated with etanercept, hydroxychloroquine, sulfasalazine, inhaled corticosteroids, and azithromycin). Stable pulmonary function was observed in the remaining 15 patients (63%) and included 1 patient with .rheumatoid arthritis (treated with prednisone, methotrexate, inhaled corticosteroids) and one patient with Sjogren syndrome (treated with prednisone, etanercept, and methotrexate).

Six patients (14%) died after a median interval of 63 months (range, 4–140 months). One patient diagnosed to have rheumatoid arthritis 2 months after presentation with CB died at 51 months of respiratory failure resulting from progressive airflow obstruction despite continued pharmacologic therapy with prednisone, mycophenolate mofetil, and inhaled corticosteroids. Five remaining deaths occurred in patients without CTD or seropositivity: 1 patient died of myocardial infarction, and the cause of death was unknown in the remaining 4 patients. Two patients (5%) who did not manifest clinical or serologic evidence for CTD underwent lung transplantation at 51 and 84 months, respectively, after the diagnosis of CB. Both patients underwent bilateral lung transplantation and remain alive at 20 and 164 months after lung transplant, respectively.