Rheumatoid arthritis-associated lung disease in black Africans: Descriptive study of 28 cases in Lomé

Background Several studies have shown that lung disease is a common extra-articular manifestation of rheumatoid arthritis (RA). Objectives To describe the lung manifestations in the RA population in Lomé, Togo. Methods The study was conducted from October 2018 to July 2019 at the pulmonology unit of the Sylvanus Olympio University teaching hospital, in collaboration with rheumatology centres in Lomé, Togo. Patients meeting the American College of Rheumatology criteria for RA were prospectively enrolled. They underwent clinical examination, spirometry, a 6-minute walk test (6MWT) and a chest X-ray (CXR). All information collected and surveys gathered were subjected to statistical analysis. Results Twenty-four out of 28 patients were women (85.7%). The mean (standard deviation (SD)) duration of illness was 4.1 (2.8) years. Thirteen patients out of 28 (46.4%) had respiratory symptoms. On CXR, interstitial lung disease was the only pleuropulmonary lesion (17.8%). Spirometry was abnormal in 25% of cases, with a predominance of restrictive ventilatory disorder (21.4%). The 6MWT was abnormal in 25% of patients. A total of 20 patients (71.4%) had at least one lung manifestation. We noted that there were significantly more patients with respiratory symptoms and no radiographical abnormalities than those with both respiratory symptoms and radiographical abnormalities (p=0.013). Conclusion Lung changes affect a significant proportion of RA patients in Lomé. Studies conducted with appropriate respiratory investigations and combining cardiovascular explorations will bring us closer to an understanding of the effects of RA-associated lung disease.


RESEARCH
of vital capacity were found in patients tested in a seated position.The measurements were obtained without the use of bronchodilators.
A 6MWT was obtained with Cosmed Spiropalm.The 6MWT was abnormal when there was desaturation of 4% and more compared with the initial saturation.Patients who did not undergo a 6MWT due to joint disease were not included in the evaluation of the 6MWT results.Those who did not undergo PFTs within 2 months of the standard CXR were also excluded from the PFTs outcome evaluation.
The plethysmography and carbon monoxide diffusing capacity (DLCO) tests were not performed due to their absence in our setting.

Chest X-ray assessment
Chest pain standard radiography was obtained with the YSX500D 500 mA digital X-ray machine.A radiologist and a pulmonologist agreed after discussing each patient's final report.The lung lesion site on the CXR was distributed based on the international classification pneumoconiosis X-rays of the International Labor Office (ILO): [15] upper-right area (URA), middle-right area (MRA), lower-right area (LRA), upper-left area (ULA), middle-left area (MLA), lower left area (LLA).
High-resolution chest computed tomography (HRCT) was not performed owing to its unavailability in our setting.

Statistical Analysis
Data were entered using EpiData 3.1 and analysed using STATA version 14 (StataCorp., USA).The χ 2 test (or Fisher's exact test if the numbers were <5) was used to compare the categorical variables.The significance limit was set at 0.05.

Results
The study considered 28 RA cases, including 4 men (14.3%) and 24 women (85.7%).The male:female ratio was 1:6.The mean age of male patients was 35.2 (6.2) years, that of female patients was 46.8 (17.0) years and that of all patients was 45.2 (16.4) years, with extremes of 10 and 75 years.With respect to age, the majority of patients (57.1%) were younger than 49 years.Half of them (50%) had a duration of illness between 1 and 3 years.The mean duration of illness was 4.1 (2.8) years, with extremes of 1 and 12 years.High blood pressure was the most common medical history (14.3%).As an immunological assessment, only antinuclear antibodies were found in 5 patients (17.8%).They were high in 1 patient (20%) and normal in 4 (80%).Rheumatoid factor and anticitrullinated protein antibodies were not found in any patient.All patients were on anti-RA therapy at diagnosis.Anti-RA drugs were administered with no respiratory examination.The majority of patients (71.4%) were taking oral prednisone associated with methotrexate (MTX), 4 (14.3%)only received non-steroidal anti-inflammatory drugs (NSAIDs), 2 (7.1%) took only MTX, 1 (3.6%) took only prednisone and 1 (3.6%) was given only salazopyrin.
Thirteen of the 28 patients had respiratory symptoms (46.4%), including shortness of breath (61.5%), dry cough (38.5%), chest pain (30.7%) and sputum production (7.7%).Under no circumstances did respiratory symptoms precede the diagnosis of RA.Only three patients (10.7%) had clinical evidence of lung involvement in the form of bronchitis and crackles.No other extra-articular symptoms were noted.
Spirometry was abnormal in 7 of the 28 patients (25%): 1 case of obstructive ventilatory disorder and 6 cases of restrictive ventilatory disorder.Abnormalities in the 6MWT were detected in 7 (25%) of the 28 patients.
Of the 28 patients, 8 had no abnormality in any of the parameters related to lung involvement.Consequently, a total of 20 patients (71.4%) had at least a lung involvement.
We noticed that patients with respiratory symptoms and no radiographical abnormality were significantly more numerous than those with both respiratory symptoms and radiographical abnormalities (Table 1).No other factor was significantly associated with chest radiographical abnormalities (Table 2).Patients aged ≥50 years had significantly longer RA duration than those of lower age (Table 3).

Discussion
As shown in our study, RA is a disease with at least a 3:1 predilection for women between 20 and 50 years of age. [16]It is often treated with prednisone or methotrexate. [17,18]

RESEARCH
In RA-associated lung diseases, respiratory symptoms, usually insidious, include dyspnoea on exertion, and a non-productive cough. [19]These symptoms are commonly seen in ILD, which is common in RA. [18] This explains why bibasilar crackles are found in most patients in various studies. [19]However, it is currently estimated that ~30% of patients with RA have subclinical ILD noted on chest high-resolution computer tomography (HRCT). [8]lso, recognition of exertional dyspnoea may be delayed due to exercise limitations associated with joint disease.As in our study, chest pain, which is often a sign of pleural disease, is less present.Pleural disease is also common in RA patients, but only 3 -5% of patients are symptomatic. [8]everal studies revealed that HRCT is much more sensitive than CXR in the evaluation of ILD, and that its higher sensitivity should allow early diagnosis. [20]HRCT was not used in our study, which constitutes a limitation.However, the CXR also allowed us to realise that interstitial bibasilar lesions were the most common.The prevalence of ILD in RA patients is about 20 -50% depending on the study method. [19,21]Concerning pleural disease, pleural thickening and/or effusion was found in between 16 and 24% in chest radiography of RA patients. [19]Also, RA-associated cardiovascular [22] disease could explain the relatively high prevalence of cardiomegaly (28.5%) in our study.
One-third of RA patients usually have abnormal pulmonary function tests (PFTs). [5]Habib et al. [5] found that 32.5% of patients in their study had abnormal PFTs.This rate was slightly different from ours (25%), most likely due to the systematic use of lung diffusing capacity for carbon monoxide (DLCO) in their study.The majority of patients with RA-ILD will have a restrictive pattern on PFTs, with or without decreased DLCO and hypoxaemia. [23]ecrement of FVC and DLCO is associated with a poorer prognosis.However, a study by Assayag et al. [6] revealed that only decreased DLCO was statistically significant.PFTs were generally poor predictors of CXR and HRCT findings. [5]ore than two-thirds (71.4%) of our patients had RA-associated lung disease, contrasting with the results of Adelowo et al., [3] where no respiratory manifestation was found in RA patients.This difference is certainly due to the lack of systematic searching for respiratory disorders in the study conducted by Adelowo et al. [3] The prevalence of pulmonary abnormalities in RA patients varies according to the characteristics of the study population, the definition of lung disease used, and the sensitivity of the clinical investigations used. [19]In unselected populations, up to one-third of subjects describe important respiratory symptoms, but two-thirds or more may have significant radiographic abnormalities on HRCT. [24]he present study showed that patients with respiratory symptoms and no radiographical abnormalities were significantly more numerous than those with both respiratory symptoms and radiographical abnormalities.This could be explained by the fact that the respiratory symptoms (dyspnoea and cough) are not specific for pulmonary damage, but may also be of cardiovascular origin. [22]Indeed, eight patients (28.5%) had cardiomegaly in our study.Such differences are less important in studies where chest HRCT was systematic [5] because the chest HRCT is much more sensitive and specific than CXR in the evaluation of ILD, [20] and ILD is the most common pulmonary manifestation of RA-associated lung disease. [18]

Table 3 . Factors influencing the duration of RA progression Duration of RA progression p-value No, n (%) Yes, n (%)
RA = rheumatoid arthritis; CXR = chest X-ray.