Pulmonary abnormalities on high-resolution comPuted tomograPhy in Patients with long standing rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is a systemic inflammatory disease, associated with a number of extra-articular organ manifestations. Pulmonary involvement is a frequent and severe extraarticular manifestations of rheumatoid arthritis. RA can affect lung parenchyma, airways and pleura. Objectives. To identify RA-related lung disease on chest computed tomography (CT). Material and methods. We performed high-resolution computed tomography (HRCT) on a total of 92 patients with longstanding RA. Results. The subjects were predominantely female (79.3%), the age at entry was 63.77 ±11.56 years, and 42.9% had a history of smoking. Disease duration was 15.00±11.55 years. Pulmonary CT abnormalities were found in 71 of the 92 patients (77.2%). The most common HRCT anomalies were: linear attenuation (reticulation) (52.11%), bronchiectasis andbronchial wall thickening (45%), nodular attenuation (39.43%) and pleural involvement (pleural effusion or thickening) (39.43%). Conclusions. We conclude that RA-related lung disease was commonly detected on chest CT imaging in longstanding RA patients.


INTRODUCTION
Rheumatoid arthritis (RA) is a systemic inflammatory disease. Its main feature is persistent, symmetrical, erosive synovitis, but a large number of extraarticular manifestations can occur in virtually any organ leading to cutaneous, ocular, hematological, cardiovascular and pulmonary lesions (1).
Pulmonary involvement occurs in 60-80% of patients with RA and can affect any component of the lung. The spectrum of rheumatoid arthritis-associated respiratory disease includes a wide range of pulmonary abnormalities: interstitial lung disease (ILD), airway disease (AD), nodules, pleural disease and vascular disease (2)(3)(4).
Prevalence rates of pulmonary abnormalities in RA reported in the literature vary widely, depending on the criteria used to define disease, methods used to detect pulmonary involvementand patient populations examined. It has been reported that RA-associated lung disease is seen more frequently in men with longstanding rheumatoid disease, in the presence of high rheumatoid factor titers and in the setting of more severe joint involvement. However, it is a subject of debate. High resolution computed tomography (HRCT) has been proven to be useful for the detection and characterization of morphological changes in the lungs of RA patients (1).

OBJECTIVE
Our aim was to investigate the prevalence and types of pulmonary involvement in patients with longstanding rheumatoid arthritis using high-resolution computed tomography scan (HRCT).
Statistical analysis was performed using SPSS 20.0 software. Numerical variables, analysed using Student t test, were expressed as mean ± SD. Categorical variables, evaluated using Chi-square test or exact Fisher test, were expressed as frequencies and percentages.

Study cohort characteristics
The subjects were predominantely female, 73 (79.3%), the mean age at entry was 63.77 ±11.56 years and 39 patients (42.9%) had a history of smoking, with a mean of 18.19±17.26 pack-years. Mean age at RA onset was 50.7 ±15.25 years and disease duration was 15.00±11.55 years. All patients had long standing disease. Anti-CCP antibody and RF were positive in 81.5% and 90.2% of the subjects, respectively. Metothrexate was the cDMARD used in 50 of our subjects (53.8%). Erosive disease was identified in 70 subjects (76.1%). Most patients were overweight or obese and mean BMI was of 29.53±28.07. Respiratory symptoms were present in 65 patients (70.7%), with exertional dyspnea being the main complaint in 59 of the cases(64.1%), followed by non productive cough in 46 patients (50%) and productive cough in 15 cases (16.3%). The X-ray abnormalities were present in 46 of cases (50%) and 71 patients (77.2%) had abnormal chest CTs (Table 1).
Pulmonary CT anomalies were correlated with respiratory symptoms and chest X-ray changes. There were no significant correlations between the presence of HRCT pulmonary lesions and the patients' demographic characteristics (age, sex, smoking history) or the RA features (disease duration, RF seropositivity, disease activity, the severity of joint involvement, methotrexate therapy) ( Table 2).
They are seconded by the CT abnormalities suggestive for airway disease (AD) (bronchial dilatation and bronchial wall thickening). Pleural changes were identified in 28 patients (39.43%): 21 cases had pleural thickening, 2 patients had an isolated pleural effusion and in 5 cases these changes coexisted. Positive high-resolution computed tomography findings are presented in the table below (Table 3).

DISCUSSIONS
Even though cardiovascular disease is the most common cause of RA-related death, pulmonary manifestations contribute significantly to morbidity, leading to a mortality of 10-20% in RA patients (3).
Our study showed that RA patients had considerable changes on chest HRCT, with higher or similar rates when compared to other studies investigating pulmonary HRCT features in patients with longstanding RA (Table 5) (2,8,10-12). The prevalence and type of pulmonary abnormalities identified on chest HRCT vary among different studies and reasons for that are: different definitions, aims and heterogeneous patient populations (Table 6) (1,2,6,8,10-12). Lack of a unitary classification leads to dissipated data. However, the lesions suggestive for airway disease (bronchial dilatation and bronchial wall thickening) are constantly present in at least 30% of the cases (30-75%). In our study, linear attenuation (reticulation), as asign of ILD, is the most frequent CT finding (52%). The Remy-Jardinet et al. 1994 cohort included 84 patients (65.47% women), with a mean disease duration of 12±8 years). Thirty eight (49%) patients had abnormal CT scans. Abnormalities identified were: bronchiectasis (30%), pulmonary nodules (22%), ground glass attenuation (14%) and honeycombing (10%) (10).
The advent of lung HRCT lead to the possibility of a more detailed assessment of lung involvement: Youssef et al., in 2012, in a series comprising nonsmokers, 34 females (94.4%) and 2 males (5.6%), with median age of 48.5 years and median disease duration of 8 years, 77.8% positive for RF, and nearly two-thirds (28/36) of the patients with one or more pulmonary symptom such as dyspnea, cough, wheezing or phlegm, yielded the following results: based on the HRCT findings, abnormalities were detected in 17 patients (47.2%). In regards to the type of pulmonary involvement detected, interstitial lung disease was the commonest as it was detected in 14 patients (38.9%). Eight patients (22.2%) had reticular opacities, while two (5.6%) had honeycombing and 4