Pattern of pulmonary function test in rheumatoid arthritis patients

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by a painful symmetrical peripheral polyarthritis. Extra-articular involvement in RA is a common condition. Pulmonary involvement occurs in 20 to 67 % of RA patients and it is responsible for about 10-20 % of mortality in RA patients. Objectives: To evaluate the extent and pattern of pulmonary involvement in RA patients by using spirometry. Methods: A case control study conducted at the rheumatology unit of Al Sader teaching hospital, forty RA patients [33(82.5%) female and 7(17.5%) male] and sixty apparently healthy subjects {50(83.3%) female and 10(16.7 %) male} were included in the study. All subjects had subjected to a pulmonary function test (PFT) for pulmonary function evaluation using MIR spirolab III. Measured and predicted forced vital capacities (FVC), forced expiratory volume in the first second (FEV1) and FEV1 / FVC ratio were considered as the parameters in this study for both groups. Results: Nine patients were found to have a restrictive pattern of pulmonary function test, while obstructive pattern was found in only one patient. On the other hand, the pulmonary function tests were normal in all of sixty healthy control. The mean of FEV1 in patient group (2.07 ± 0.56L) and of FEV1% (95.8%  25.2) are significantly lower than those in the control group (2.46 ± 0.65 L; 105.3%  13.09). In addition, mean FVC in the patient group (2.35 ± 0.62L) and its mean percentage (92%  22.68) showed a clear significant reduction compared to those in control group (2.71 ± 0.67 L; 100.53  12.12). No significant difference (P = 0.173) has been observed in FEV1 / FVC ratio between patient (88.17  7.47) and control group (89.87  4.99). Conclusions: Different pattern of pulmonary function abnormalities could be manifested in RA patients and the restrictive pattern represents the most common feature. Spirometry is indicated as a baseline assessment and for follow up of RA patient to enhance early detection and management of the pulmonary involvement.

The prevalence of RA is approximately 0.5-1% worldwide with some variability among different populations, [2] in Iraq it is prevalence is 1%. [3]Highest prevalence was recorded in Pima Indians and Chippewa Indians, whereas the lowest in Japan and China. [4,5]Rheumatoid arthritis more commonly occurs in females than in males with age related differences.Younger onset RA female to male ratio is 4.4:1 while in elderly onset RA, the ratio is 1.6:1. [6]Extra-articular involvement in RA is common.It was recorded in 51% of 587 RA Italian patients, and the manifestation was more common in males patients, in positive antinuclear antibody and in rheumatoid factor positive patients. [7]In addition to rheumatoid nodules, other organs could be involved in the disease process includeing heart, lung, blood vessels, peripheral nerves as well as hematological involvement.The occurrence of extra-articular pulmonary manifestation of RA ranges from 20 % in some studies to as high as 67% in others. [8,9]Respiratory airways, pleura, lung parenchyma and vascular compartment all may be attacked by RA. [10] In the majority of RA patients, arthritis develops first, whereas in others, pulmonary involvements could proceed or simultaneously occur with arthritis. [11]ifferent forms of interstitial lung disease (ILD) occur in RA patients.They are a group of heterogenous paranchymal lung disorders characterized by their clinical, pathological and radiological features. [12]The most commonly observed ILD in RA patients are usual interstitial pneumonia, nonspecific interstitial pneumonia and inflammatory airway disease with organizing pneumonia pattern. [11]It has been estimated that pulmonary complications are responsible for 10-20% mortality in RA patients which is mostly caused by ILD. [13]

OBJECTIVES
The aim of this study is to evaluate the extent and abnormality of pulmonary function test in RA patients by using spirometry.

SUBJECTS AND METHODS
This study is a case control study done at the rheumatology unit in Al Sader teaching hospital during the period from June 2011 to October 2011.Spirometry was used as a diagnostic test to evaluate the type and the severity of pulmonary involvement in RA patients.After detailed and thorough medical history and physical examination, forty newly and previously diagnosed patients of both genders (82.5% female and 17.5% male) who met RA 2010 classification criteria as described by American College of Rheumatology were included in our study. [14]Patients age is ranging R from 13 to 67 (mean 48.5) years.Another sixty healthy subjects (83.3% female and 16.7% male) were included in the study as a control group, their age ranges from 13 to 64(mean 46.1) years.Both groups were matched for height, weight and race.Patients with history of smoking, drug intake, past medical history of respiratory, cardiac and other chronic diseases were excluded from the study.All subjects had further subjected to a pulmonary function test (PFT) for their pulmonary function evaluation using spirolab-III (MIR-Italy).The test was carried out in a sitting position according to the standard protocol with the best record out of three attempts was considered for further data analysis.Measured and predicted forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and FEV1 / FVC of RA and control groups were analyzed in our study.Data analysis were carried out using SPSS software version V.20, t test and Fisher exact test were and the data were expressed as mean ± standard deviation (mean ± SD), P ≤ 0.05 was considered significant.

DISCUSSION
The results of this study show that the number of RA female patients exceed that of male patients seen within same time frame with a ratio reached to as high as 4.7:1.Although this results is a little higher value than what has been reported in the other populations, [3] it is consistent with worldwide reports that demonstrate a tendency of RA disease for female gender.It has been found that rheumatoid arthritis improves during treatment with estrogen-containing oral contraceptives, pregnancy and with estrogen replacement therapy which suggest the role of sex hormone in developing RA in such a higher rate in females. [16]Abnormal pulmonary function test has been found in 25% of RA patients.A restrictive pulmonary features found in nine patients (22.5%), ranging from mild features in six patients (15%) moderate severity in two patients (5%) to severe restrictive features in one patient (2.5%).Only one patient (2.5%) showed obstructive pulmonary features.Our results show a tendency of RA as a systemic inflammatory condition to attack pulmonary tissues as an early common extra articular target of the disease process.A comparable data has been reported by a study in which abnormal pulmonary function test has been observed in 30% of 246 RA patients. [17]In addition, the overall patients data compared to the matched control group shows a significant decrease in the average FEV1and FVC among RA patients with no significant changes in FEV1/FVC.These results indicate a restrictive lung pattern of interstitial lung disease that does not affect the bronchial resistance and tone but lung volumes.Our finding of abnormal pulmonary function tests in RA patients rises the question of time at which pulmonary tissues are attacked by RA autoantibodies.It has been found by data from other studies that systemic inflammation and autoimmunity may precede the presentation of RA as a classifiable disease. [18]Deane et al 2010 found elevated levels of autoantibodies, cytokines and chemokines in a stored blood samples obtained from 73 military cases with seropositive RA in the preclinical stage of RA. [19] Whereas van de Sande et al 2011 could not find any histological or magnetic resonance imaging (MRI) evidence of synovial inflammation in the knee of individuals with seropositive RA-related autoantibodies without clinically-evident synovitis. [20], Demoruelle and his colleagues recently observed a higher prevalence of inflammatory airways disease using computed tomographic imaging in arthritis-free with seropositive RA-related autoantibodies compared to a seronegative matched controls. [21]In a consistent cross sectional study for characterizing pulmonary involvement in 63 RA patients by spirometer, xray and high resolution computed tomography (HRCT) of thorax, Mohd et al 2009 found a restrictive pattern of pulmonary disease in 66.7% of the patients.The most common HRCT findings were reticulation (46%), ground glass opacities (38.1%) and bronchiectasis (28.6%). [22]The limitations in our study includes small sample size, the inability to show the disease activity in correlation with pulmonary involvement by using rheumatoid factor, anticitrullinated peptides (CCP) antibody levels and x-ray changes as well as diffusion lung capacity for carbon monoxide (DL CO ) test as an indicator of the severity of respiratory membrane involvement.
In conclusion, the lung is a potential target organ of the RA inflammatory disease process that could precede the onset of the synovial joint involvement.Different pattern of pulmonary function abnormalities could be manifested in RA patients and a restrictive pattern represents the most common feature.Spirometry test is indicated as a baseline assessment and follow up for RA patient to enhance early detection and management of the pulmonary involvement.

Table 1 . General characteristics of RA and control groups.
), a total of 100 individuals of both sex were selected in our study, 40 RA patients and 60 healthy individuals.As illustrated in (Table-1) there was no significant difference in sex distribution between RA patients and control groups (P = 0.56).The mean age of RA group (48.5  10.4 year) was not significantly different (P = 0.205) from the mean age of control group (46.1  8.2 year).Moreover, no significant difference (P = 0.344) was observed between the mean height of RA group (159.5  7.3 cm) and control group (161  8.1cm).