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Lung Diseases Directly Associated with Rheumatoid Arthritis and Their Relationship to Outcome

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Lung Diseases Directly Associated with Rheumatoid Arthritis and Their Relationship to Outcome Eur Respir J 2011; 37: 1411–1417 DOI: 10.1183/09031936.00019210 CopyrightßERS 2011 Lung diseases directly associated with rheumatoid arthritis and their relationship to outcome Y. Tsuchiya*, N. Takayanagi*, H. Sugiura#, Y. Miyahara*, D. Tokunaga*, Y. Kawabata" and Y. Sugita* ABSTRACT: The outcome and cause of death of each lung disease directly associated with AFFILIATIONS rheumatoid arthritis (RA-LD) have been poorly investigated. Depts of *Respiratory Medicine, #Radiology, and A retrospective study was conducted of 144 patients with RA-LD, in whom the median follow-up "Pathology, Saitama Cardiovascular period after the initial visit for a respiratory examination was 4.5 yrs. and Respiratory Center, Kumagaya, A total of 57 patients were identified with usual interstitial pneumonia (UIP), 31 with Japan. bronchiectasis, 16 with nonspecific interstitial pneumonia (NSIP), 11 with bronchiolitis, five with CORRESPONDENCE organising pneumonia (OP), five with diffuse alveolar damage (DAD) and 19 with combined disease. Y. Tsuchiya The 5-yr survival rates were 36.6% in the UIP group, 87.1% in the bronchiectasis group, 93.8% in the Dept of Respiratory Medicine NSIP group, 88.9% in the bronchiolitis group, 60.0% in the OP group and 20.0% in the DAD group. Saitama Cardiovascular and Survival of patients with DAD was worse than that of patients with UIP. Overall, survival of patients Respiratory Center 1696 Itai with UIP was worse than that of patients with bronchiectasis, NSIP or bronchiolitis. Of the 144 Kumagaya patients, 71 (49.3%) died, of whom 58 (81.7%) died due to respiratory lesions. Saitama 360-0105 Of patients with RA-LD, patients with DAD experienced the highest mortality, and the survival of Japan patients with UIP was worse than that of patients with NSIP. E-mail: caeser-salad.2corn-soups@ nifty.com KEYWORDS: Bronchiectasis, bronchiolitis, diffuse alveolar damage, nonspecific interstitial Received: pneumonia, rheumatoid arthritis, usual interstitial pneumonia Feb 04 2010 Accepted after revision: Sept 20 2010 First published online: heumatoid arthritis (RA) is a destructive Overall, the standardised mortality ratios of RA Sept 30 2010 systemic inflammatory disorder. In addi- patients are reported as 1.27–2.26 [7, 8]. Excess R tion to the impact RA has on the joints, mortality was seen in RA patients with infection, pulmonary involvement occurs regularly, and lymphoma, gastroenterological disorder, cardio- is responsible for a significant portion of the vascular disease and pulmonary fibrosis [7, 8]. morbidity and mortality associated with RA [1]. Causes of death in RA patients were cardiovas- Although pulmonary infection, drug toxicity or cular disease in 31%, respiratory disease in 22%, both are frequent complications, lung disease solid tumours in 20%, cerebrovascular disease in directly associated with RA (RA-LD) is the most 10% and other reasons in 17% [8]. common [1]. RA-LD includes: interstitial lung In the idiopathic interstitial pneumonias (IIPs), the diseases such as usual interstitial pneumonia histological pattern seen on surgical lung biopsy is (UIP), nonspecific interstitial pneumonia (NSIP), the most important predictor of early mortality [9]. organising pneumonia (OP) and diffuse alveolar In RA-LD, the prognosis of UIP [2, 5, 10–12], NSIP damage (DAD); airway diseases such as bronch- [11, 12], OP [2], DAD [2], bronchiectasis [13], iectasis and bronchiolitis; pleuritis; pulmonary bronchiolitis [5, 14] and interstitial lung fibrosis vascular disease; and rheumatoid nodules [1, 2]. [15] has been reported, but the relationship be- The prevalence of the different disease patterns tween the individual disease types and outcome of RA-LD has been reported previously [2–6]; has not been fully investigated. Furthermore, patterns specific to UIP, NSIP, OP, bronchiectasis whether the causes of death in patients with RA- and bronchiolitis were commonly seen on surgi- LD are similar to those in all RA cohorts must be cal lung biopsy and/or high-resolution com- clarified. Thus the aims of the present study were puted tomography (HRCT), but DAD was quite to retrospectively review RA patients with RA-LD, uncommon. However, the difference in clinical document any differences in clinical features European Respiratory Journal features of patients with each type of disease has between the various disease types, assess impact Print ISSN 0903-1936 c been poorly investigated. on prognosis and analyse causes of death. Online ISSN 1399-3003 EUROPEAN RESPIRATORY JOURNAL VOLUME 37 NUMBER 6 1411 LUNG INVOLVMENT OF SYSTEMIC DISEASE Y. TSUCHIYA ET AL. METHODS was approved by the institutional review board of Saitama Study subjects Cardiovascular and Respiratory Center. During the 10 yrs from April 1996 to March 2006, 277 patients Diagnostic criteria for RA-LD with pleuropulmonary complications of RA were treated at the Saitama Cardiovascular and Respiratory Center (Kumagaya, Diagnosis of RA-LD was based on the following criteria. A total of 24 patients were diagnosed on the basis of histology Japan) (fig. 1). Of these patients, 119 were not included because (two with bronchiectasis were diagnosed by lobectomy, 14 by their lung disease, such as pulmonary infection, drug-induced surgical lung biopsy, three by autopsy and the remaining five pneumonia or lung cancer, was not directly associated with by transbronchial biopsy), and 120 were diagnosed on the basis RA. Seven patients with UIP were excluded because they of clinico-radiological features. Pathological diagnosis of in- had simultaneous lung cancer, two because the pathological terstitial pneumonia obtained from surgical lung biopsy or diagnosis obtained from surgical lung biopsy was unclassifi- autopsy was made using the consensus classification for IIPs able interstitial pneumonia and five because there were less [17]. In some patients with classic clinical and radiological than five patients with the same disease type. The remaining features of OP or DAD, diagnosis of these diseases was 144 patients comprised the cohort of the present study. Patients confirmed by the histological pattern seen in a bronchoscopic were followed-up until March 2009 or until death before biopsy specimen [17]. Follicular bronchiolitis (FB) was diag- March 2009. All patients fulfilled the revised criteria for RA of nosed when prominent peribronchiolar lymphoid follicles the American Rheumatism Association [16]. The present study with a germinal centre were present [18]. Bronchiolitis ob- literans (BO) or constrictive bronchiolitis was diagnosed if there was pathological evidence of bronchiolar luminal Rheumatoid arthritis patients with pulmonary complications (n=277) narrowing or occlusion by scarring [18]. The pathological diagnoses in the 24 patients included: UIP (n53); NSIP (n54); OP (n52); DAD (n53); FB (n51); BO (n51); FB and BO (n53); bronchiectasis (n52); OP and FB (n52); UIP and FB (n51); UIP, NSIP and FB (n51); and UIP, OP and pleuritis (n51). RA-LD (n=158) Other lung disease (n=119) Standard HRCT protocols were used to obtain images for Pulmonary infections (n=81) evaluation. Collimation was ,2.0 mm in all images, and all were COPD (n=26) Lung cancer (n=11) reconstructed using high-resolution algorithms. Computed Drug-induced pneumonitis (n=9) tomography (CT) scans were obtained at suspended end- Asthma (n=7) inspiratory effort with the patients in the supine position. The Pneumoconiosis (n=4) scans were reviewed independently in a blinded fashion by two Sarcoidosis (n=1) observers (N. Takayanagi and H. Sugiura), and were interpreted Hypersensitivity pneumonitis (n=1) on the basis of previously published data [4, 6]. Scans consistent Bronchial atresia (n=1) with UIP contained predominant basilar reticulation, traction bronchiectasis and honeycombing. Scans consistent with NSIP Patients with UIP and lung cancer contained predominant bibasilar ground-glass attenuation with excluded (n=7) limited reticulation and honeycombing was absent. Scans consistent with OP contained patchy airspace consolidation associated with ground-glass attenuation. Scans consistent with Patients with unclassifiable IP DAD contained patchy or diffuse ground-glass attenuation excluded (n=2) associated with airspace consolidation, and may have shown intralobular reticulation or traction bronchiectasis. Scans con- sistent with bronchiolitis contained centrilobular and/or peri- Patients with RA-LD excluded bronchial nodules, branching linear structures and mosaic because the disease group perfusion with bronchial dilatation. Each observer noted the comprised <4 patients (n=5) most appropriate diagnosis for each patient. In cases of Pleuritis (n=2) Patients included in study (n=144) DIP (n=1) disagreement, consensus was obtained following further review. UIP (n=57) LPD (n=1) DAD was distinguished from acute exacerbation of UIP, which Bronchiectasis (n=31) Pulmonary nodules (n=1) NSIP (n=16) was included in UIP [19]. Since FB and BO can coexist in the Bronchiolitis (n=11) airways [14], they were regarded together as bronchiolitis. Some OP (n=5) patients with combined disease were included in the combined DAD (n=5) group. Patients who had UIP and bronchiectasis together were Combined disease (n=19) not considered to have traction bronchiectasis caused by UIP but rather bronchiectasis limited to one or multiple lobes. FIGURE 1. Flow diagram showing patients with lung disease directly associated Study design with rheumatoid arthritis (RA-LD). COPD: chronic obstructive pulmonary disease; The case records of 144 patients with
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