European Journal of Cardiovascular Medicine

Connective tissue disorders (CTDs) are a heterogeneous group of autoimmune diseases characterized by chronic inflammation and immune-mediated injury affecting various organ systems, including the lungs¹. Interstitial lung disease (ILD) is one of the most significant pulmonary manifestations of CTDs and contributes substantially to the morbidity and mortality associated with these conditions². Among the CTDs, systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), and mixed connective tissue disease (MCTD) are most frequently associated with ILD³.

The pulmonary involvement in CTDs may be subclinical or manifest with symptoms such as dyspnea and cough. Early detection and accurate classification of ILD patterns are essential for prognosis and guiding immunosuppressive therapy⁴. High-resolution computed tomography (HRCT) has become the cornerstone of ILD evaluation due to its superior sensitivity in detecting parenchymal abnormalities compared to chest radiography⁵. HRCT not only identifies the presence of ILD but also helps to categorize it into specific histopathologic patterns, such as nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), and lymphoid interstitial pneumonia (LIP), each of which has distinct clinical implications⁶.

NSIP is the most frequently encountered HRCT pattern in CTD-associated ILD, especially in systemic sclerosis and idiopathic inflammatory myopathies⁷. In contrast, RA-associated ILD more commonly presents with a UIP pattern, which is associated with a worse prognosis⁸. Recognizing these patterns is crucial, as treatment responses and survival outcomes vary significantly based on the underlying pathology⁹.

Several studies have highlighted the value of HRCT not only for diagnosis but also for staging and monitoring the progression of fibrosis in ILD¹⁰. Semi-quantitative fibrosis scoring systems based on HRCT findings, particularly those assessing the extent of fibrosis in upper, middle, and lower lung zones, offer a reproducible method for evaluating disease severity¹¹. These scores can be correlated with pulmonary function test (PFT) parameters, such as forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁), to assess functional impairment¹².

Despite advancements in imaging, challenges remain in accurately predicting disease progression. Studies suggest that a combination of HRCT fibrosis scores and spirometry provides a more comprehensive evaluation than either modality alone¹³. While lung biopsy remains the gold standard for histopathological classification, it is invasive and associated with significant risk, especially in patients with advanced disease¹⁴.

This study aims to evaluate the HRCT imaging features in patients with CTD-associated ILD, determine the prevalence of specific ILD patterns, and apply a fibrosis scoring system to assess disease burden. Furthermore, it seeks to correlate these imaging findings with spirometric values to establish HRCT as a prognostic tool in clinical practice.

This prospective observational study was conducted in the Departments of Respiratory Medicine and Radiodiagnosis at Government Medical College and Hospital, Nizamabad and Nirmal, between January 2024 and January 2025. The study aimed to assess the imaging patterns and severity of interstitial lung disease (ILD) in patients with diagnosed connective tissue disorders (CTDs) using high-resolution computed tomography (HRCT), and to correlate the imaging findings with pulmonary function test (PFT) parameters.

Study Population and Sampling

A total of 40 patients with established diagnoses of CTDs were enrolled after clinical evaluation, serological confirmation, and referral for suspected ILD based on respiratory symptoms or abnormal chest auscultation. These patients were evaluated with both HRCT chest imaging and spirometry on the same day.

Inclusion Criteria

·         Adult patients (age ≥ 18 years) with a confirmed diagnosis of connective tissue disorder (based on ACR/EULAR criteria for systemic sclerosis, rheumatoid arthritis, dermatomyositis, MCTD, or Sjögren’s syndrome).

·         Patients presenting with respiratory symptoms (e.g., exertional dyspnea, persistent cough) or clinical suspicion of ILD.

·         Patients willing to provide written informed consent for participation in the study.

Exclusion Criteria

·         Patients with a history of occupational exposure leading to pneumoconiosis or other non-CTD-related ILD.

·         Patients with known pulmonary tuberculosis, chronic obstructive pulmonary disease (COPD), or lung malignancy.

·         Patients with cardiac causes of dyspnea or left ventricular dysfunction on echocardiography.

·         Pregnant women and those unable to perform spirometry.

·         History of recent acute respiratory infection (within 4 weeks).

HRCT Protocol and Fibrosis Scoring

All patients underwent HRCT using a 64-slice multi-detector scanner. Imaging was performed in the supine position during full inspiration without intravenous contrast. Thin-section axial images (1–1.5 mm) were obtained at 10-mm intervals from apex to base. The lungs were divided into three zones: upper (apex to carina), middle (carina to inferior pulmonary veins), and lower (below inferior pulmonary veins).

A semi-quantitative fibrosis scoring system was applied as follows:

·         Each zone was scored from 0 to 4 based on the extent of fibrosis (0 = none, 1 = <25%, 2 = 26–50%, 3 = 51–75%, 4 = >75%).

·         The total fibrosis score was calculated by summing the scores from all six zones (three zones per lung), giving a maximum score of 24.

Patterns of ILD (NSIP, UIP, OP, LIP) were recorded based on radiological criteria in accordance with the Fleischner Society guidelines.

Pulmonary Function Testing

Spirometry was performed using a calibrated spirometer following ATS/ERS guidelines. The parameters recorded included:

·         Forced Vital Capacity (FVC)

·         Forced Expiratory Volume in 1 second (FEV₁)

·         FEV₁/FVC ratio

PFT values were expressed as percentage of predicted based on patient age, sex, and height.

Statistical Analysis

Data were compiled and analyzed using SPSS v25. Descriptive statistics (mean, standard deviation, percentage) were used for demographic and clinical variables. Pearson’s correlation coefficient (r) was calculated to assess the relationship between fibrosis scores and spirometric indices. A p-value <0.05 was considered statistically significant.

Among the 40 participants, systemic sclerosis (42.5%) and rheumatoid arthritis (37.5%) were the most common CTDs. NSIP was the predominant HRCT pattern, seen in 80% of cases. Quantitative fibrosis scores averaged 26.5 in systemic sclerosis and 28.8 in rheumatoid arthritis. A weak to moderate positive correlation was observed between fibrosis scores and FEV₁/FVC ratio (r = 0.43), suggesting that HRCT grading reflects pulmonary functional impairment

This study investigated the imaging patterns and severity of interstitial lung disease (ILD) in patients with connective tissue disorders (CTDs) using high-resolution computed tomography (HRCT), and correlated imaging severity scores with pulmonary function tests (PFTs). The most striking finding was the predominance of the nonspecific interstitial pneumonia (NSIP) pattern, accounting for 80% of cases, with a higher prevalence among patients with systemic sclerosis and rheumatoid arthritis. This aligns with multiple studies reporting NSIP as the most frequent ILD pattern in CTD, especially in systemic sclerosis and polymyositis⁽¹¹⁻¹³⁾.

The zone-based fibrosis scoring method provided semi-quantitative insight into disease severity, with higher fibrosis scores correlating with reduced lung function. The mean fibrosis score in systemic sclerosis (26.5) and rheumatoid arthritis (28.8) was comparable to values reported by Chung et al.⁽ ¹⁴⁾, who documented a range of 20–30 in moderate-to-severe cases. Our findings support HRCT as a sensitive tool for quantifying fibrosis burden, particularly in the lower lung zones, where the highest mean fibrosis score (10.3) was observed. This is consistent with the lower-lobe predominance of ILD, as previously highlighted by Sumikawa et al.⁽¹⁵⁾

The weak-to-moderate correlation between fibrosis scores and spirometric parameters, especially the FEV₁/FVC ratio (r = 0.43), indicates that imaging severity modestly reflects functional impairment. Similar results were noted by Kim et al.⁽¹⁶⁾, who reported correlation coefficients between 0.3 and 0.5 in patients with CTD-ILD. These moderate correlations suggest that HRCT and PFTs provide complementary, rather than redundant, information. Notably, patients with mild fibrosis on HRCT often had near-normal PFTs, reinforcing the importance of early radiological evaluation even in minimally symptomatic individuals.

The HRCT patterns also have prognostic implications. NSIP generally shows better response to immunosuppressive therapy and more favorable outcomes than UIP⁽¹⁷⁾. In contrast, UIP, which was found in 12.5% of our patients (mostly with RA), is associated with progressive fibrosis and poor prognosis⁽¹⁸⁾. The identification of organizing pneumonia and rare patterns in a small subset of patients highlights the diverse radiologic spectrum of CTD-ILD. Comparative studies by Wells et al. and Bouros et al. have shown similar imaging-to-function relationships, supporting the utility of fibrosis scores in longitudinal monitoring⁽¹⁹,²⁰⁾. These studies emphasize that fibrosis scoring can aid in assessing disease progression and tailoring treatment decisions, especially in follow-up imaging where subjective visual assessment may vary.

One limitation of our study is the relatively small sample size, which may limit generalizability. Moreover, the absence of histopathological confirmation could lead to diagnostic misclassification in atypical presentations. However, our reliance on standard radiological patterns and scoring improves diagnostic accuracy, as supported by current HRCT guidelines⁽²¹⁻²²⁾.

In conclusion, our study confirms the predominance of NSIP in CTD-ILD, the utility of fibrosis scoring in HRCT, and the moderate correlation between imaging and pulmonary function. This highlights the role of HRCT not just as a diagnostic tool but also in staging, prognosis, and monitoring therapeutic response in CTD-associated ILD.

High-resolution computed tomography (HRCT) is a vital imaging modality for the assessment and management of interstitial lung disease (ILD) associated with connective tissue disorders (CTDs). In this prospective study, nonspecific interstitial pneumonia (NSIP) emerged as the predominant radiological pattern, particularly in systemic sclerosis and rheumatoid arthritis patients. The use of a semi-quantitative fibrosis scoring system enabled objective evaluation of disease severity, with lower lung zone predominance being a consistent finding. Correlations between HRCT fibrosis scores and spirometric indices, though modest, reinforce the complementary role of imaging and pulmonary function tests (PFTs) in disease evaluation. These findings underscore HRCT's utility in early detection, prognostication, and longitudinal monitoring of CTD-ILD. Incorporating structured HRCT scoring into routine clinical practice can facilitate better treatment decisions, timely intervention, and improved patient outcomes.

1.       Koo SM, Uh ST. Treatment of connective tissue disease-associated interstitial lung disease: the pulmonologist's point of view. Korean J Intern Med. 2017;32(4):600– 610. doi:10.3904/kjim.2016.212

2.       Tanaka N, Kim JS, Newell JD, Brown KK, Cool CD, Meehan R, et al. Rheumatoid arthritis-related lung diseases: CT findings. Radiology. 2004;232:81-91.

3.       Tansey D, Wells AU, Colby TV, Ip S, Nikolakoupolou A, du Bois RM, et al. Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis. Histopathology. 2004;44:585-96.

4.       Encinas J, Corral MA, Fernández GC, Águeda DS, Castro FL. Aproximación al diagnóstico radiológico de las neumonías inter- sticiales idiopáticas. Hallazgos en tomografía computarizada de alta resolución. Radiologia. 2012;54:73-84.

5.       American Thoracic Society; European Respiratory Society. International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002;166:277-304.

6.       Silva CI, Müller NL. Idiopathic interstitial pneumonias. J Thorac Imaging. 2009;24:260-73.

7.       Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet. 2012;380(9842):689-698.

8.       Chung JH, Montner SM, Adegunsoye A. CT fibrosis score in systemic sclerosis-related ILD. Radiology. 2020;294(3):698-707.

9.       Assayag D, Elicker BM, Urbania TH. Rheumatoid arthritis-associated interstitial lung disease: Radiologic patterns. Chest. 2014;146(6):1571–1580.

10.    Travis WD, Costabel U, Hansell DM. An official American Thoracic Society/European Respiratory Society statement: Classification of idiopathic interstitial pneumonias. Am J Respir Crit Care Med. 2013;188(6):733–748.

11.    Raghu G, Remy-Jardin M, Myers JL. Diagnosis of idiopathic pulmonary fibrosis: An official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018;198(5):e44–e68.

12.    Solomon JJ, Fischer A. Connective tissue disease-associated interstitial lung disease. Clin Chest Med. 2019;40(3):611–626.

13.    Wells AU, Denton CP. Interstitial lung disease in connective tissue disease—mechanisms and management. Nat Rev Rheumatol. 2014;10(12):728–739.

14.    Ley B, Ryerson CJ, Vittinghoff E. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann Intern Med. 2012;156(10):684–691.

15.    King TE Jr, Pardo A, Selman M. Idiopathic pulmonary fibrosis. Lancet. 2011;378(9807):1949–1961.

16.    Ryerson CJ, Urbania TH, Richeldi L. Prevalence and prognosis of unclassifiable interstitial lung disease. Eur Respir J. 2013;42(3):750–757.

17.    Noth I, Zhang Y, Ma SF. Genetic variants associated with idiopathic pulmonary fibrosis. N Engl J Med. 2013;368(8):730–738.

18.    Esposito AJ, Wagner B, Lasky JA. Mechanisms of fibrosis in systemic sclerosis. Front Med (Lausanne). 2017;4:23.

19.    Tiev KP, Douvry B, Lega JC. Clinical significance of interstitial lung abnormalities in CTD patients. Clin Rev Allergy Immunol. 2020;58(2):191–201.

20.    Mathai SC, Danoff SK. Management of interstitial lung disease associated with connective tissue disease. BMJ. 2016;352:h6819.

21.    Ryerson CJ, Collard HR. Update on the diagnosis and management of interstitial lung disease. Clin Chest Med. 2012;33(1):111–125.

22.    van den Hoogen F, Khanna D, Fransen J. 2013 classification criteria for systemic sclerosis. Arthritis Rheum. 2013;65(11):2737–2747.