European Journal of Cardiovascular Medicine

Rheumatoid arthritis (RA) is systemic progressive autoimmune disorder, impacting approximately 1-2% of the global population (1). It is a systemic inflammatory condition that may affect various tissues and organs in addition to the synovial joints.

Lung is most common site of extra articular disease, lung manifestation of RA includes airways, parenchymal, vascular and pleural disease. The development of lung abnormalities in RA normally occurs after the onset of articular disease, although in some cases lung involvement is the first sign of the disease and is its most severe symptoms.

Pulmonary disease accounts for 10-20% of all mortality in patients with rheumatoid arthritis (2). The potential for pulmonary disease in all RA patients should therefore never be overlooked by clinicians.

Spirometry is an important tool for classifying lung diseases broadly into restrictive or obstructive lung processes as well as screening for and monitoring pulmonary diseases.

The carbon monoxide diffusing capacity (DLCO), also known as the transfer factor (TLCO), which measures the rate of carbon monoxide (CO) transfer from the lung to the blood, is the most often used test of gas transfer across the lung after arterial blood gas measurements. The reduction in diffusing lung capacity of carbon monoxide reported was suggested to be an early indicator for the presence of both restrictive and obstructive disease of lung.

Spirometry and DLCO in Rheumatoid arthritis patients help in early detection and reduces the complication and mortality in rheumatoid arthritis patients.

Previous work has suggested an association between lung disease development and RA activity and inflammation. Peripheral blood parameters (erythrocyte sedimentation rate, C reactive protein, rheumatoid factor and anti‑citrullinated peptide autoantibodies) and scales of articular involvement, such as DAS-CRP 28, were evaluated for RA activity.

AIMS AND OBJECTIVES OF THE STUDY

1. Primary Objective: To study the patterns of Pulmonary function abnormalities using spirometry and DLCO in Rheumatoid arthritis patients.
2. Secondary objective: To correlate spirometry abnormalities with rheumatoid arthritis disease activity.

RHEUMATOID ARTHRITIS

The first clinical description of Rheumatoid Arthritis is credited to Lander- Beauvais (Paris, 1800), but it was Alfred Baring Garrod (1859) who first used the term “Rheumatoid” arthritis. Rheumatoid Arthritis is a chronic inflammatory, systemic disease that produces its most prominent manifestations in the diarthrodial joints.

The most common form of the disease is demonstrated by symmetrical, destructive and deforming polyarthritis affecting small and large synovial joints with associated systemic disturbances, in addition to a variety of extraarticular features and the presence of circulating antiglobulin antibodies. RA most frequently affects people between the ages of 25 and 55 and is more common in women higher than in men (2.5:1); however, males tend to experience extra-articular manifestations of the disease more frequently. These manifestations can arise at any age following the initial onset of RA.

The pathophysiology of rheumatoid arthritis (RA) is characterized by the infiltration of T-lymphocytes, B-lymphocytes, and monocytes into the synovial membrane of various joints throughout the body.

Macrophages release pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and interleukin-6 (IL-6), which contribute to the damage of adjacent bone and cartilage.

The causes of rheumatoid arthritis are complex and multifactorial. Genetic predisposition significantly contributes to the likelihood of developing RA, increasing the risk by three to nine times. The HLA-DRB1 (Human Leukocyte Antigen DR Beta 1) region is closely linked to the presence of anti-cyclic citrullinated peptide antibodies (ACPA) in positive RA cases.

Around 50% of patients with rheumatoid arthritis exhibit various extra-articular manifestations of the disease. The condition is marked by destructive polyarthritis along with involvement of various extra-articular organs, which may include the skin, eyes, heart, lungs, kidneys, nervous system, and gastrointestinal tract. Rheumatoid arthritis is associated with a high risk for morbidity and premature death secondary to the earlier development of cardiovascular, lung diseases and malignancy

Patients diagnosed with rheumatoid arthritis and presenting high levels of rheumatoid factor—autoantibodies directed against the Fc segment of immunoglobulin G—are more likely to develop extra-articular symptoms associated with their disease.

EXTRA ARTICULAR MANIFESTATION OF RHEUMATOID ARTHRITIS:

Skin- Rheumatoid nodules, Raynaud’s phenomena, palmar erythema, peripheral ulcers, cutaneous vasculitis.

Pleuropulmonary-Pleuritis, pleural effusion, rheumatoid lung nodules, small airway disease, interstitial lung disease.

Eyes- Scleritis, episcleritis, keratoconjunctivitis sicca.

Cardiovascular- Atherosclerosis, pericarditis, Myocardial infraction, arrhythmias, valvular heart disease.

Neurological - Entrapment neuropathy, mononeuritis multiplex, cervical subluxation.

Musculoskeletal-Osteoporotic changes, tendon, and ligament rupture.

Renal-Glomerulonephritis, secondary amyloidosis.

Hematological -Felty’s syndrome, Large granular lymphocyte syndrome, anemia, thrombocytosis.

Vascular- Vasculitis.

The diagnosis of rheumatoid arthritis (RA) can be difficult in the early stages due to the diverse clinical manifestations and the absence of universally accepted pathognomonic tests.

American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) in 2010 are widely used for diagnosis 2010 ACR/EULAR Classification Criteria for RA ⁽³⁾.

Systemic inflammatory markers such as CRP and ESR have been positively correlated with declining pulmonary function, reinforcing the hypothesis that chronic inflammation plays a pivotal role in RA-associated lung disease progression. Inflammatory markers include an increased erythrocyte sedimentation rate and heightened C-reactive protein levels, both of which correlate with disease activity.

Disease activity score in 28 joints calculated with C-reactive protein is used to look for disease activity in rheumatoid arthritis. It was categorized as high disease activity with DAS28 score > 5.1, moderate disease activity score > 3.2 to < 5.1, low disease activity score > 2.6 to < 3.2 and remission with score of < 2.6⁽⁴⁾.

PULMONARY MANIFESTATION OF RA ⁽⁵⁾

1. Interstitial lung disease
   • Usual interstitial pneumonia
   • Nonspecific interstitial pneumonia
   • Organizing pneumonia
   • Lymphocytic interstitial pneumonia
   • Acute interstitial pneumonia
2. Airways disease
   • Follicular bronchiolitis
   • Constrictive bronchiolitis (obliterative bronchiolitis)
   • Bronchiectasis
   • Cricoarytenoid arthritis
3. Rheumatoid nodules
4. Pleural disease
   • Pleuritis
   • Pleural effusion
   • Pneumothorax
   • Empyema
5. Vascular disease
   • Pulmonary hypertension
   • Vasculitis
6. Rheumatoid pneumoconiosis (Caplan syndrome)
7. Drug toxicity
8. Amyloidosis

INTERSTITIAL LUNG DISEASE:

Interstitial lung disease (ILD) is among the most common and thoroughly researched respiratory complications associated with rheumatoid arthritis.

The development of RA-ILD is not yet completely understood; however, genetic and environmental factors are crucial in the emergence of interstitial lung disease among those with rheumatoid arthritis.

Major contributors to the risk of developing RA-ILDs include smoking, advanced age, male sex, high-titer anti-cyclic citrullinated peptide antibodies, elevated rheumatoid factor, and genetic factors.

HLA-DRB1, HLA-DR4, and HLA-B40 are important HLA variants that contribute to the development of interstitial lung diseases in patients with rheumatoid arthritis ^(6).

The role of imaging is vital in diagnosing RA-ILDs. Initial assessments typically include chest radiographs and high-resolution computed tomography (HRCT), which are used to identify the distribution and patterns of interstitial parenchymal abnormalities.

Early diagnosis of RA-ILD is associated with a marked decrease in the progression of the disease.

AIRWAY INVOLVEMENT

Airway disease is highly prevalent among individuals with rheumatoid arthritis, affecting approximately 39% to 60% of patients (7). It can involve any section of the airway, including both the upper and lower large airways as well as the distal small airways. Common clinical presentations include bronchiectasis, bronchiolitis, airway hyperreactivity, and cricoarytenoid arthritis. To diagnose airway involvement, spirometry and high-resolution computed tomography with expiratory images are effective. Cricoarytenoid arthritis and bronchiectasis are the most common forms of large airway involvement.

PLEURAL INVOLVEMENT

Pleural involvement is a common pulmonary manifestation of rheumatoid arthritis, with small pleural effusions noted in up to 70% on autopsy studies. However, only about 3–5% of patients are symptomatic ⁽⁸⁾. Most effusions are unilateral, although occasionally bilateral effusions are found. Fever and pleuritic chest pain are common, but cough is generally absent unless there is comorbid parenchymal lung disease.

RHEUMATOID NODULES

Rheumatoid nodules can be either singular or numerous, predominantly situated in the pleural or subpleural regions, and may occasionally show signs of cavitation. Uncomplicated nodules may spontaneously regress or improve with standard rheumatoid arthritis therapy.

SPIROMETRY:

Spirometry is a physiological test that measures the maximal volume of air that an individual can inspire and expire with maximal effort. The primary signal measured in spirometry is either volume or flow as a function of time.

Spirometry is an important tool for classifying lung diseases broadly into restrictive or

obstructive lung processes as well as screening for and monitoring pulmonary disease.

Spirometry is performed according to established guidelines set by organizations like the American Thoracic Society (ATS) and the European Respiratory Society (ERS), which ensure standardized procedures for patient instruction, equipment calibration, and data interpretation, considering factors like age, height, and gender to determine normal lung function values ⁽⁹⁾.

Vital capacity (VC): The volume change between the position of full inspiration and complete expiration.

Forced vital capacity (FVC): The maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration.

Forced expiratory volume (FEV₁): The maximal volume of air exhaled with maximally forced effort in 1 second.

FEV₁/FVC ratio: The ratio of FEV₁ to FVC expressed as a percentage; FEV₁/FVC is the most used measure.

INTERPRETATION OF SPIROMETR

The results included the percentage of predicted forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), as well as the categorization of the spirometric pattern into restrictive or obstructive types and the associated severity levels measured by spirometry.

Figure 1 – (A) Flow- volume curve (B) Volume -time curve ⁽¹⁰⁾.

The smooth lines, expiratory time of greater than six seconds, and quick peak of the peak expiratory flow rate indicate a good spirometric effort.

TYPES OF SPIROMETRY ABNORMALITIES:

FIGURE -2

The three major patterns of flow. Spirograms and flow volume curves are shown which were obtained in a patient with a restrictive ventilatory defect (top), a normal subject (middle), and a patient with an obstructive ventilatory defect (bottom) ^(11).

Table -1 Severity grading of Restriction (FVC)

Table -2 -Severity grading of Obstruction ⁽¹²⁾

DLCO:

The diffusing capacity of the lung for carbon monoxide, also referred to as the transfer factor

of the lung for carbon monoxide, is used to evaluate the transfer of gas from the alveolar

 air spaces into the pulmonary capillaries. It can be measured when known and very low concentrations of carbon monoxide (CO) are inspired. Expressed in mL/min/mm Hg or mmol/min/kPa, the DLCO represents the volume of CO (in mL) transferred per minute for each unit of pressure difference (in mm Hg) across the total available functioning gas exchange surface in the lungs. The 10-second, single-breath-holding technique is the most widely used. It was introduced by Marie Krogh in 915, and later refined by Forster and coworkers, Ogilvie and coworkers, and McGrath and Thomson ⁽¹³⁾. 10-second, breath-holding with a rapid response gas analyzer and no alveolar sample bag/chamber is mostly commonly used. In this technique, the patient inhales a volume of test gas containing 0.3% methane or other tracer gas, 0.3% CO, 21% O2, and the balance N2. Again, the test gas is held in the lungs for approximately 10 seconds, and then during exhalation the tracer gas and CO concentrations are analyzed continuously by a rapid response gas analysis ⁽¹⁴⁾.

Table -3 -DLCO SEVERITY GRADING ⁽¹⁵⁾

Study design: The present study was conducted from April 2023 for a period of 1 year in SDM medical college and hospital in tertiary center. This study was a cross- sectional study on spirometry and diffusing capacity of lungs for carbon monoxide findings in Rheumatoid arthritis patients.

Sampling

1. Sampling population - Sample size -117
2. Sample size calculation was done using formula n=Z²Pq/d²
3. Where Z =Standard normal variate value

Precision(d)=Margin of error =9% P=Expected proportion =0.45 P=45%, q=100-45%=55%

Inclusion criteria:

Patients aged more than 18 years of age who are diagnosed as Rheumatoid arthritis by ACR /EULAR (American College of Rheumatology /European League Against Rheumatism) classification criteria.

Exclusion Criteria:

1. Mixed connective tissue disorder
2. Tuberculosis
3. Bronchial asthma
4. Chronic obstructive pulmonary disease
5. Pulmonary vascular disease
6. Those with critical illness

The study was conducted after obtaining clearance from Institutional Ethics Committee. A written informed consent form was obtained from all study participants. A thorough history was obtained. Demographic and clinical data were collected. All patients underwent a comprehensive physical and respiratory examinations .Patients with positive RF, anti CCP ,or both were considered to have seropositive RA. Information regarding rheumatoid factor (RF),anti -CCP ,erythrocyte sedimentation rate (ESR),C reactive protein (CRP),and the current and past use of disease modifying antirheumatic drugs was collected from their medical records .The severity of disease activity was measured using the DAS 28 CRP score which considers 28 tender and swollen joint counts, general health (patient assessment of disease activity using a 100 mm visual analogue scale), CRP levels.

In all of the patients, spirometry and DLCO were performed using NDD Easy One Pro model, and the results and severity of PFT abnormalities were interpreted as per the American Thoracic society /European Respiratory Society guidelines.

Chest X ray was obtained with a digital radiography system in posterior- anterior view, at

maximum inspiration. The CXR images were analyzed and were assessed for the presence

of lung abnormalities.

Statistical Methods

Descriptive statistics was used (mean, Standard deviation, frequency and percentage), Karl pearson correlation coefficient was used to find test to find direction of a linear relationship between qualitative variables, chi-square test was used to find association between two categorical variables..

Table:4 Age wise distribution of patients

Age wise distribution of patients 117 Rheumatoid arthritis patients were included in the  study. Mean age was 46.73 ± 13.28.

Table -5 -Gender wise distribution of patients

In this study 18 patients (15.38%) were male,99 patients were female (4.62%).

Table: 6 -Duration of disease wise distribution of patients

Duration of RA A total of 64.96 % (76 patients) had been diagnosed with RA for 1–5 years

Table: 7 - Parameter of disease activity in RA patients

Results of Spirometry abnormalities in Rheumatoid arthritis

Patients Table: 8 -Type of spirometry abnormalities

Patterns of spirometry abnormalities among RA patients 90 RA patients had normal spirometry parameters, and 27 patients (23.07%) had spirometry abnormalities. 19 patients had restrictive pattern, and 3 patients had obstructive pattern ,5patients had mixed pattern.

Table: 9 Severity of obstructive patterns

In 3 obstructive pattern 1 patient had mild ,1 had moderate ,1 had severe obstruction.

Table: 10-Severity of Restrictive patterns

In 20 restrictive pattern 12 patients had mild restrictive pattern and 7 patients had moderate restrictive pattern.

Table: 11- DLCO severity grading

The tests also showed decreased diffusing Lung capacity for carbon monoxide (DLCO) in 23 (17.94%) patients.

In 23 abnormal DLCO 5 patient had mild 7 (4.57%) ,11 patient had moderate (9.40%),5 patient had severe (4.57%) impairment.

Table: 12- Correlation between DLCO and DAS-CRP 28 scores by Karl Pearsons correlation coefficient.

Figure: 3- Scatter diagram of correlation between DLCO and DAS-28 CRP scores

Correlation between DAS CRP 28 and DLCO

There was a negative correlation between DAS -CRP 28 and DLCO(r value = -0.26).

Table: 13- Correlation between FVC and DAS-28 CRP scores by Karl Pearsons correlation coefficient

Figure: 4- Scatter diagram of correlation between FVC and DAS-28 CRP scores

Correlation between DAS -CRP 28 and FVC

There was a negative correlation between DAS-CRP 28 and FVC (r=-0.22).

Table: 14- Prevalence of symptoms among abnormal spirometry patients (n=27)

In 27 abnormal spirometry patients 18 (66.67%) patients had cough.

In 27 abnormal spirometry patients 20 (74.0%) patients had breathlessness.

Table 15- Chest XRAY findings

Out of 27 abnormal spirometry 10 patients had bilateral reticular opacity ,4 patients had emphysematous changes,1 patient had pulmonary nodule ,4 patient had bronchiectasis

Table :16 Extra articular involvement (n=117)

Out of 117 RA patients 6 (5.12%) patients had extraarticular involvement ,1 patient had episcleritis ,2 had osteoporosis ,2 had Raynaud phenomenon,1 had keratoconjunctivitis sicca.

This cross-sectional study was aimed to assess the spirometry abnormality of RA patients meeting the 2010 RA ACR/EULAR criteria and correlation of disease activity with spirometry abnormalities.

DEMOGRAPHIC AND DISEASE PROFILE

Rheumatoid arthritis is commonly recognized as a chronic inflammatory disease that predominant affects women. In our study majority of patients were female- to-male ratio with 5:1, probably the main factor leading to the development of rheumatoid arthritis in females is the variation in sex hormone levels, particularly estrogen and progesterone, which are crucial in regulating inflammation.

The mean age in our study 46.73 ± 13.2 indicating that the studied population falls in middle age group, were RA often manifests.

DURATION OF DISEASE AND SPIROMETRY ABNORMALITY

The duration of rheumatoid arthritis (RA) is an important factor determining extraarticular manifestations. In our analysis, we found that most of the patient’s duration of RA was 1 - 5 years (64.96%), with mean of 4.94 yrs these findings were consistent with the study by Das MP et.al (16).

In our present study, no significant relation was found between the duration of disease and spirometry abnormalities. Similar observation was noted by Madhavan S (17).

SPIROMETRY ABNORMALITY

Spirometry is the most common and most useful lung function test. This finding has extensive clinical implications. It is the least expensive test to perform, and it should be the test most widely available in doctors’ offices, clinics and hospitals.

In our study spirometry abnormalities were detected in 27 patients out of 117 RA patients , with restrictive patterns being the most common( 16.24%) patients, followed by obstructive patterns (2.56 % )and mixed (5 %) this aligns with studies conducted by Avon LS et.al(18) which concluded that restrictive ventilatory defect as the most prevalent spirometry abnormality in RA patients ,among 19 patients with restrictive pattern ,12 patients had mild restriction and 7 patients have moderate restriction ,and among 3 patients with obstructive disease 1patient had mild,1 patient had moderate ,1 patient severe obstruction.

Among 117 patients 7 were unable to perform DLCO test and DLCO was reduced in 23 (17.94%) patients, suggestive of diffusion limitation in RA patients, among 23 patients

 with abnormal DLCO, 7 patients had mild,11 patients had moderate, and 5 patients had

severe reduction of DLCO.

CORRELATION OF SYMPTOMATOLOGY WITH SPIROMETRY ABNORMALITY

In our study RA patients with spirometry abnormality, symptoms such as cough were reported in 66.67% patients, breathlessness was reported in 74.0% patients though not statistically significant but still emphasizing the need for proactive screening in RA patients with spirometry and DLCO in those having respiratory symptoms.

CORRELATION OF DISEASE SEVERITY WITH SPIROMETRY ABNORMALITY

There was a negative correlation seen between the FVC and DAS CRP 28 scoring and also a negative correlation between DLCO and DAS CRP 28 scoring, which align with similar studies by Tisher, M et.al (2021) (19). which showed that RA patients with higher DAS28-CRP scores showed a trend towards worse pulmonary function, especially with restrictive lung patterns. Although the correlation was not statistically significant, it suggested that inflammation could play a role in the development of pulmonary dysfunction in RA patients.

In our study predominantly patients had a normal chest Xray. Among cxray abnormalities reticular opacities was evident in (8.55 %), followed by emphysematous changes (3.42%), bronchiectasis evident in (3.42%), pulmonary nodule in one patient. These findings are in concordance with previous study by Kumar et .al (20) where normal chest X-ray was seen in a significant proportion of patients, which highlights the fact that chest Xray cannot be solely used for screening RA patients for pulmonary abnormalities.

Other Extra-Articular Manifestations

Other Extra-articular involvement other than pulmonary involvement was relatively low (5.12%), 1 patient had episcleritis,2 had osteoporosis, and 2 had Raynaud’s phenomenon and 1 had keratoconjunctivitis sicca, the lower rate observed in our study might be attributed to the relatively shorter disease duration in most of our patients.

In our study, we selected spirometry as an indicator of lung function abnormalities because they represent a widely accepted and low-risk diagnostic tool that frequently precedes radiographic evaluation in clinical practice.

The study identified pulmonary dysfunction in participants who had symptoms, which implies that all rheumatoid arthritis (RA) patients with symptoms should undergo spirometry for a comprehensive pulmonary evaluation. Spirometry is recommended for RA patients as a baseline assessment and for ongoing follow-up to enhance the early detection and management of pulmonary involvement. RA patients may exhibit various lung function impairment patterns, including obstruction, restriction and also mixed patterns.

We identified a negative correlation between the severity of rheumatoid arthritis and the occurrence of lung involvement. Though not statistically significant but still crucial to assess lung involvement in RA patients with higher disease activity, even in the absence of respiratory symptoms.

DAS-CRP28 SCORE indicates disease activity in RA. Therefore, a high DAS CRP Score at  baseline may indicate high disease activity and may correlate with the decline in lung function due to the lung involvement in RA patients.

LIMITATIONS

Our study was a cross-sectional study, and patients were not followed up. It was a single center study. HRCT is considered the gold standard for pulmonary involvement in RA, which was not performed in our study. We could not compare our study findings with duration of anti-rheumatoid medications

SUMMARY

Rheumatoid arthritis is a chronic autoimmune inflammatory condition. Pulmonary involvement is a common and significant extra-articular manifestation, associated with a poor prognosis, patients with Rheumatoid Arthritis are at risk for pulmonary complications, which can significantly impact their mortality and morbidity rates.

This cross-sectional study conducted in diagnosed RA patients aimed to study the patterns of Pulmonary function abnormalities using spirometry and DLCO in Rheumatoid arthritis patients and correlate spirometry abnormalities with rheumatoid arthritis disease activity.

Spirometry and DLCO are low risk, non-invasive, economical and reproducible better diagnostic tool for measuring lung function in RA patients.

Spirometry and DLCO abnormalities were predominantly seen in patients with respiratory symptoms and there was a negative correlation between RA disease activity and lung function. Spirometry revealed abnormal patterns, with predominant restrictive pattern than obstructive pattern.

It is important for RA patients to undergo regular spirometry and DLCO to facilitate early diagnosis of pulmonary involvement especially in those with respiratory symptoms and those with high disease activity and also to manage disease progression effectively.

However larger, multi-center and longitudinal studies even incorporating HRCT chest would provide more detailed insights into subclinical and early pulmonary changes in RA patient.

1. Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD, Tanasescu R. Extra-articular manifestations in rheumatoid arthritis. J Clin Med. 2010;5(4):286-291
2. Esposito AJ, Sparks JA, Gill RR, et al. Screening for preclinical parenchymal lung disease in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(8):3234- 3245.
3. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an ACR/EULAR collaborative initiative. Arthritis Rheum.2010;62(9):2569–81.
4. Butt A, Raja KM, Awan FJ, et al. Comparison of disease activity by DAS28-CRP and DAS28-    ESR in RA. Pak J Pathol. 2024;35(3):116–23.
5. Shaw M, Collins BF, Ho LA, et al. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015;24(135):1–16.
6. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365:2205–19.
7. Geddes DM, Webley M, Emerson PA. Airways obstruction in RA. Ann Rheum 1979;38(3):222–5.
8. Balbir-Gurman A, Yigla M, Nahir AM, et al. Rheumatoid pleural effusion. Semin Arthritis Rheum. 2006;35(6):368–78.
9. Graham BL, Steenburggen I, Miller MR, et al. Standardization of spirometry 2019 Am J Respir Crit Care Med. 2019;200(8): e70–e88.
10. Crapo RO. Pulmonary-function testing. N Engl J Med. 1994;331(1):28.
11. Broaddus VC, Mason RJ, Ernst JD, et al., editors. Murray and Nadel’s textbook of respiratory medicine. 7th ed. Philadelphia: Elsevier; 2021.
12. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for COPD 2024 report.
13. McGrath MW, Thomson ML. Effects of age, body size and lung volume on DLCO. J Physiol. 1959; 146:572–82.
14. Huang YC, Macintyre NR. Real-time gas analysis improves DLCO measurement. Am Rev Respir Dis. 1992;146(4):946–50.
15. Pellegrino R, Viegi G, Brusasco V, et al. Strategies for interpreting lung function tests. Eur Respir J. 2005;26(5):948–68.
16. Das MP, Gogoi B, Alam MR. Clinical profile of pulmonary manifestations in RA. Int J Sci Res. 2020;9(12):1–3.
17. Madhavan S, Kingsley CT, Anandan H. Correlation of pulmonary function with RA disease activity. Int J Cont Med Res. 2017;4(9):2000–3.
18. Avnon LS, Manzur F, Bolotin A, et al. Pulmonary function testing in RA patients. Isr Med Assoc J. 2009;11(2):83–7.
19. ishler M, et al. Systemic inflammation and pulmonary function in RA. J 2021;48(5):736–41.
20. Kumar D, Achari V. Pulmonary manifestations in RA: clinical and radiological findings. J Evid Based Med Healthc. 2020;16(3):248–52