Clinical Rheumatology

, Volume 30, Issue 2, pp 217–221

Pulmonary involvement in early rheumatoid arthritis patients

Authors

    • Department of Rheumatology and RehabilitationMansoura University
  • Ashraf A. Eisa
    • Department of RadiodiagnosisBani Sweef University
  • Waleed R. Arafat
    • Department of Chest Disease and TuberculosisBani Sweef University
  • Mohamed A. Marie
    • Internal Medicine Dept, Faculty of MedicineCairo University
Original Article

DOI: 10.1007/s10067-010-1492-5

Cite this article as:
Habib, H.M., Eisa, A.A., Arafat, W.R. et al. Clin Rheumatol (2011) 30: 217. doi:10.1007/s10067-010-1492-5

Abstract

Pulmonary involvement in rheumatoid arthritis (RA) is common and can be due to the disease itself as well as to the therapies used to treat it. The purpose of this study was to disclose the pulmonary involvement in early RA patients not more than 2 years disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment. Forty patients aged 37.6 ± 10.3 with early rheumatoid arthritis not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their RA with DAS28, which was utilized for disease activity determination. Ten percent of our patients were found to be clinically involved by interstitial lung disease (ILD), where 27% have abnormal HRCT finding and 32.5% with abnormal PFT. Predilection for clinically manifest ILD was evident in active RA patients with high DAS28 score, seropositive RA patients, and in patients receiving steroids and anti-TNFα therapy. ILD occurs early in the course of RA, with more predilection for clinically active RA disease.

Keywords

Early RAPulmonary involvement

Introduction

Rheumatoid arthritis is a common systemic disease that manifests as inflammatory arthritis of multiple joints and produces a wide variety of intrathoracic lesions. Pleuritis is frequent with pleural effusion [13]. Rheumatoid pulmonary nodules are an asymptomatic finding in seropositive rheumatoid arthritis (RA) [4]. Diffuse interstitial alveolitis is rare [57]. Methotrexate may also associate with the development of fibrosis [4].

Many articles have studied the lung involvement in rheumatoid arthritis, yet sparse works explore how early the pulmonary involvement happens in rheumatoid patients.

The purpose of this study is to disclose the pulmonary involvement in early RA patients with not more than 2 years’ disease duration using the computed tomography (CT) as well as the pulmonary function tests as a method of pulmonary involvement assessment.

Materials and methods

Patients

Forty patients with early rheumatoid arthritis—not more than 2 years of disease duration—who were fulfilling the revised criteria for rheumatoid arthritis of the American Rheumatism Association [8] were recruited for the study. They were selected from the Rheumatology outpatient clinic of Al Ahsa Hospital, Ahsa, Saudi Arabia with the collaboration of other three rheumatology clinics in three central hospitals in the district. Mean duration of disease was 18 ± 3.2 months. An informed consent was obtained for every patients participating. They were collected over a period from July 2007 to February 2009.

Clinical assessment

For clinical assessment of disease activity in all of our patients, a disease activity score with reduced joint count (DAS28) has been used [11]. A cut-off point of DAS28 ≤ 3.2 has been proposed that patient is in clinical remission [9, 12] with values >5.1 representing high disease activity [13].

Full clinical chest examination was done to find out any symptoms or signs suggestive of interstitial lung disease (ILD).

Pulmonary function tests

Spirometry was performed according to American Thoracic Society guidelines [10]. Vital capacity, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio with cut-off level 70%, total lung capacity, and maximum expiratory flow at 25% of vital capacity, 50% of vital capacity, and 75% of vital capacity were determined, with subjects tested in the sitting position. Lung diffusing capacity for carbon monoxide (DLCO) and DLCO corrected for alveolar volume (DLCO/VA) were measured. Measurements were obtained without bronchodilator administration. The patients who did not undergo pulmonary function tests within 2 months of the CT examination were excluded from the evaluation of pulmonary function test results.

CT assessment

CT scans were obtained with Philips machine one slice. Continues scans were obtained with 1–1.5-mm collimation. CT scans were reconstructed with high spatial–frequency algorithm. CT scans were obtained at suspended end-inspiratory effort with the patient in supine position and without intravenous material.

Interpretation of CT scans

The features of interstitial lung disease by HRCT included septal lines, reticulations, traction bronchiectasis, cyst formation, and ground glass appearance. Images were read by two radiologists blindly. They know that patients have RA without other information regarding the patients. Agreement was done between the two radiologists after discussion with final reports for every patient.

Definition of lung affection using the quantitative scale [15, 14]:
  • Grade 0: normal

  • Grade 1: minimal disease = 3–4 septal lines

  • Grade 2: mild disease = >5 septal lines, reticulations, subpleural cysts, and ground glass appearance

  • Grade 3: moderate disease = grade 2 findings with traction bronchiectasis, per-bronchovascular thickening with one third to two thirds lung involvements

  • Grade 4: sever disease = grade 2 or 3 findings with more than two thirds involvement of the lung

Patient classification

Patients were classified into three groups according to presence and type of abnormality as follows:
  • Group 1—clinically significant ILD if they had (1) symptoms or signs not explained by other disease, (2) HRCT evidence of ILD of any grade above 0, and (3) any abnormalities in pulmonary function tests; diffusion, obstructive, or restrictive

  • Group 2—abnormalities compatible with ILD but no clinically significant ILD if they had (1) no clinical findings of pulmonary affection, plus (2) HRCT evidence of ILD, or (3) abnormal pulmonary function tests

  • Group 3—no abnormality compatible with ILD if none of the abnormalities described above were present

Statistical analysis

Data were analyzed using SPSS version 10. Student’s t test was used to compare clinical parameters with both the pulmonary function tests as well as CT findings (parametric) or Wilcoxon rank sum test (nonparametric) for continuous variables and chi-square analysis for categorical variables were used. Multivariate regression analysis, which included the non-continuous, was used to make relationships between variables of significant parameters.

The DAS28 is calculated using the results of the 28 tender joint counts (TJC 28) and the 28 swollen joint counts (SJC 28), ESR, and general health (GH) using:
$$ {\hbox{DAS28 - 4 = 0}}{.56}\sqrt {{\left( {\hbox{TJC28}} \right)}} + 0.28\sqrt {{\left( {\hbox{SJC28}} \right)}} + 0.70{\hbox{1n}}\left( {\hbox{ESR}} \right) + 0.014\left( {\hbox{GH}} \right). $$

Results

The study group comprised 40 patients with mean age of 37.6 years ± 10.3 that ranged from 27 to 57 years. Twelve of our patients were men and 28 were women. Out of the 40 patients, five only were cigarette smokers (one heavy and four mild smokers, and all are men). From patients’ files, none had chronic respiratory symptoms. At time of examination, four patients were having symptoms and signs of ILD evident clinically. Demographic characteristics of the patients are summarized in Table 1.
Table 1

Demographic characteristics of the patients

Total number

40

Gender: male/female

12/28

Age (years)

37.6 ± 10.3

Smoking

 

 Smoker (1 heavy, 4 mild)

5 (12.5%)

 Non-smoker

35 (87.5%)

Clinical ILD symptoms and signs

4 (10%)

Medications for RA (DMARDs)

40 (100%)

 Methotrexate

33 (82.5%)

 Prednisolone

4 (10%)

 Antimalarial

10 (25%)

 Leflunamide

10 (25%)

 Anti-TNFα

3 (7.5%)

DAS28

 

 Remission [1.8 ± 0.5]

29 (72.5%)

 Active [5.1 ± 0.9]

11 (27.5%)

Determination of RA activity status

According to DAS28 cut-off point of DAS28 ≤ 3.2 of disease remission, our patients are divided into two groups: those whose DAS28 is ≤ 3.2 with the name “Remission” group and those whose DAS above 3.2 were collected together to be named “Active” group.

Lung involvement in patients

Out of our 40 RA patients, four (10% of total number of patients) were found to have clinical symptoms and signs with abnormal PFT and HRCT related to ILD. Total number of pulmonary involvement was 18 (45%), detected by clinical manifestations of ILD, abnormal PFT, and/or HRCT findings. Eleven (27.5%) patients showed abnormal findings in HRCT. Thirteen patients (32.5%) showed abnormalities in their PFT. Out of the 13 patients with abnormal PFT, eight (20% of total number of patients) patients have abnormal HRCT findings, while five (12.5% of total number of patients) patients have abnormal PFT without any abnormalities in HRCT out of the eight patients with common PFT and HRCT abnormalities. Table 2 illustrates these results.
Table 2

Lung involvement in patients (40 patients)

Total no. of involved patients

18 (45%)

Abnormal findings in HRCT

11 (27.5%)

Abnormal PFT

13 (32.5%)

 With findings in HRCT

8 (20%)

 Without findings in HRCT

5 (12.5%)

Abnormal HRCT and PFT with clinical manifestations of ILD

4 (10%)

Pulmonary function test abnormalities

Abnormal lung functions were detected in 32.5% of the total group (13 patients). Only three patients (7.5%) showed obstructive ventilatory dysfunction. Restrictive ventilatory dysfunction was present in eight (20%) patients. All of the 13 patients showed diffusion involvement.

HRCT abnormalities

As mentioned before, abnormal HRCT findings suggestive of ILD were detected in 11 (27.5%) patients. Twenty-nine cases were of grade 0 quantitative scale of HRCT lung affection. All of the 11 affected patients were classified as grades 1 and 2 with no patients in grade 3 or 4. Four out of the 11 were grade 1, while seven were found to be grade 2. All HRCT abnormalities were located either subpleural or at the lower lung lobe. Involvement was found to be bilateral, affecting both lower lung lobe and sublpleural in two patients out of the 11 with abnormal HRCT findings.

Clinical interrelationships

According to the above-mentioned “Patient classification”, there was a statistically significant collection of cases with RF positivity, higher DAS28 score “active RA patients” and cases treated with steroid and TNFα in group 1 patients with higher predilection for ILD compared with group 2 and group 3 patients with less chance of having ILD. A significant collection of cases under antimalarial medication are in groups 1 and 2. For smoking, although the only heavy smoker patient lies in group 1, this is not a statistically validated number to consider as a statistical result. There are no other statistical significant data in other variables between groups of patients. Table 3 illustrates that.
Table 3

Correlates some of the clinical findings of the patients according to the three main groups of classification of patients

 

Group 1 (n = 4)

Group 2 (n = 14)

Group 3 (n = 22)

Age (years)

37.5 ± 3.5

40 ± 5.7

38.5 ± 6.7

Gender: male/female

1/3

4/10

7/22

Smoking (n = 5)

   

 Heavy (n = 1)

1

  

 Mild (n = 4)

 

2

2

RF+ve (number) [% within the group]

3 [75%]*

4 [28.5%]

7 [31.8%]

RA activity status; DAS28

5.3 ± 0.8**

2.2 ± 1.1

1.8 ± 0.9

RA medications “DMARDs” (number) [% within the group]

   

 Methotrexate

4 [100%]

11 [78.5%]

17 [77.3%]

 Steroid

3 [75%]***

1[7%]

0 [0%]

 Antimalarials

0 [0%]

8 [57%]****

17 [77.3%]****

 Leflunamide

1 [25%]

3 [21.5%]

5 [22.7%]

 Anti-TNFα

3 [75%]***

1 [7%]

0 [0%]

*p = 0.01 group 1 vs groups 2 and 3; **p = 0.02 group 1 vs groups 2 and 3; ***p = 0.01 group 1 vs groups 2 and 3; ****p = 0.01 groups 2 and 3 vs group 1

Discussion

Although considered a “joint disease,” RA is associated with the involvement of extra-articular manifestation [21]. Pulmonary involvement in RA is common and can be due to the disease itself as well as to the therapies used to treat it. In fact, lung disease is the second most common cause of death, following infection, for patients with RA and has been reported to affect between 1% and 40% of patients [19].

A wide range of studies have published pulmonary involvement in patients with RA with evidence-proven findings by HRCT as well as lung physiology studies, yet little have been done for early RA disease. Emerging data of our results emphasized that 10% of our early RA patients have definitive lung involvement by ILD. A total of 45% of our patient has an element of pulmonary involvement. Those patients may develop “manifest” ILD in due course of their RA disease. Further longitudinal study may be required to follow up those patients to detect any clinical manifestation of conversion to clinically manifest ILD. Also, we showed that patients who were active for their seropositive RA and are usually necessitating steroid and higher level of DMARD like anti-TNFα, with erosive kind of RA, were the patients that developed clinically overt ILD. In comparison with our findings, Bernadette et al. concluded that cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD [18]. A longitudinal study to trace all kinds of patients in the three groups may reveal a better idea about the course of ILD particularly in groups 2 and 3 with no clinical evidence of chest involvement.

Although smoking was expected to play an evident role as a predictor for ILD, and most of the literatures highlight its role, we cannot rely on our results for that issue.

In agreement with our study, Gabby et al. summarized that abnormalities consistent with ILD were found in one or more investigations in 21 of 36 (58%), which were in lung physiology in 22%, CXR in 6%, HRCT in 33%, bronchoalveolar lavage in 52%, and 99mTc-DTPA nuclear scan in 15% of patients with RA of less than 2-year duration. As noticed, they used variable ways of detection of ILD, which may yield more sensitive results than those depending only on clinical findings, HRCT, and PFT. These figures are comparable with our findings. A difference in the predictors for clinically overt ILD is noted with our results. They found no significant predictor of clinically significant ILD except male gender [16].

Very close to our results, the study of Chung et al. and Vergenenegre et al. support high incidence of airway obstructive disease in RA patients. They explore that the possibility of early airway obstruction was evident in 16 out of 33 patients with a percentage of 48.5%. They demonstrate that thin-section CT scan mainly expiratory supplement the clinical diagnosis of airway involvement in RA [17]. Also, Bernadette et al. revealed that 33% having RA without dyspnea or cough had a preclinical ILD identified by HRCT [18, 20].

We can conclude that ILD occurs early in the course of RA. There was a clear predilection of ILD with cases that were active seropositive RA, using steroid and anti-TNFα, with erosive kind of RA. Finally, we have to mention that many articles have explored the pulmonary involvement in RA patients by different means, yet few were found to disclose this involvement as early as the first 2 years of illness. In this view, we still miss much data to compare our findings with, and we need further studies with a wider sample size to confirm our findings.

Disclosures

None.

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© Clinical Rheumatology 2010