Clinical Profile of Connective Tissue Disease- related Interstitial Lung Diseases at a Tertiary Care Center in Western India

Connective tissue disorders (CTDs) are one of the common causes of interstitial lung diseases (ILDs). This prospective observational study included around 51 patients of CTD-ILDs, and their demographic, clinical, radiological, and laboratory profiles were studied. The most common type of CTD-ILD in our study is rheumatoid arthritis-related ILD. On high-resolution computed tomography (HRCT) thorax, nonspecific interstitial pneumonia (NSIP) was the most common pattern seen in 30 patients (59%), followed by usual interstitial pneumonia (UIP) seen in 20 patients (39%). Even though CTD-ILDs are similar to other idiopathic ILDs in clinical and radiological presentation, patients with CTDs have to be evaluated clinically and radiologically for early diagnosis. Early treatment initiation and pulmonary rehabilitation help in delaying the progression of disease. Among all ILDs, CTD-ILDs are associated with better prognosis and survival

Factores asociados al desarrollo de enfermedad pulmonar intersticial en esclerosis sistémica / Factors associated with the development of interstitial lung disease in patients with systemic sclerosis

Resumen Introducción: el compromiso pulmonar intersticial se presenta en 80% de las tomografías de tórax de pacientes con esclerosis sistémica (ES) y tiene gran impacto en la morbimortalidad. El objeti vo de este trabajo fue describir factores asociados al desarrollo de enfermedad pulmonar intersticial (EPI) en pacientes con diagnóstico de ES de nuestra división. Métodos: Se realizó un estudio retrospectivo, casos y controles, de pacientes seguidos entre 2005-2021 que cumplían criterios de ES. Se definió EPI al hallazgo de manifestaciones intersticiales en tomografía de tórax con cortes de alta resolución (TACAR): patrón neumonía intersticial no específica (NINE) o neumonía intersticial usual (NIU), y/o hallazgos en pruebas de función pulmonar (CVF menor al 80% y DLCO menor al 80%). Se identificaron pacientes con EPI (casos) y sin ella (controles). Se analizaron variables demográficas, clínicas y serológicas. Se calcularon medidas de porcentaje, media (DS) y mediana (RIQ) en cada variable. Se efectuó análisis univariado y multivariado, mediante regresión logística para establecer su asociación con EPI. Resultados: Se incluyeron 79 pacientes con ES, 31 con EPI. El análisis univariado demostró que el subtipo de esclerosis (según clasific ación Le Roy), las medidas de función pulmonar y positividad del anticuerpo anticentrómero fueron factores asociados en forma estadísticamente significativa con EPI. En el análisis multivariado solo la presencia de anticuerpos anti-centrómero fue estadísticamente significativa. Discusión: el análisis de los factores de riesgo para determinar desarrollo y progresión de daño pulmonar tiene vital importancia para una implementación temprana del tratamiento, lo que impactaría en la tasa de mortalidad de los pacientes con ES.

Abstract Introduction: interstitial lung involvement occurs in 80% of chest CT scans of patients with systemic sclerosis (SS) and has a great impact on morbidity and mortality. The aim of the study was to describe factors associated with the development of interstitial lung disease (ILD) in patients diagnosed with SS in our division. Methods: a retrospective case-control study of patients followed up between 2005-2021 who met the classification criteria for SS was performed. ILD was defined as the finding of interstitial manifestations on high-resolution chest tomography (HRCT): non-specific interstitial pneumonia pattern (NSIP) or usual interstitial pneumonia (UIP), and/or findings on pulmonary function tests (FVC less than 80% and DLCO less than 80%). Patients with ILD (cases) and without it (controls) were identified. Demographic, clinical and serological variables were analyzed. Percentage, mean (SD) and median (IQR) measurements were calculated for each variable. A univariate and multivariate analysis was performed using logistic regression to establish its association with ILD. Results: Seventy nine patients with SS were included, 31 with ILD. Univariate analysis showed that sclerosis subtype (according to Le Roy classification), lung function measures, and anticentromere antibody positivity were factors associated with ILD in a statistically significant way. In the multivariate analysis, only the presence of anti-centromere antibodies was statistically significant. Discussion: the analysis of risk factors to determine the development and progression of lung damage is of vital importance for an early implementation of treatment, which would impact the mortality rate of patients with SS.

Interstitial Lung Disease in Rheumatoid Arthritis: A Prospective Study at a Tertiary Care Center

Objective: The objective of this study was to evaluate the presence of interstitial lung disease (ILD) in rheumatoid arthritis (RA) and to determine the role of clinical, spirometry, and high-resolution computed tomography (HRCT) findings to facilitate early detection of ILD in RA. Materials and methods: This is a prospective study at a tertiary care hospital from February 2016 to June 2019. All patients satisfying the American College of Rheumatology (ACR) criteria for RA and having respiratory symptoms or signs were included. All patients had detailed history, clinical examination, laboratory evaluation, spirometry, and HRCT chest. Results: A total of 280 patients of RA with respiratory symptoms were evaluated, out of which 82 (29.29%) had pulmonary involvement. There were 70 women and 12 men. Rheumatoid factor was positive in 90.2% of patients while anti-CCP antibody was positive in 43.9%. Chest X-ray (CXR) showed bilateral haziness in 36.9%. HRCT findings revealed a usual interstitial pneumonia (UIP) pattern in 73.2% patients and 24% had an nonspecific interstitial pneumonia (NSIP) pattern. Spirometric evidence of lung involvement was present in 84.2% of these cases. 2D Echo showed pulmonary hypertension (PH) in 46.3% of patients. Conclusion: Screening for respiratory symptoms and signs is essential in the clinical evaluation of RA. CXR, HCRT chest, and spirometry can be used effectively to diagnose RA-ILD early.

HISTOLOGICAL SPECTRUM OF NON-NEOPLASTIC LESIONS IN THE LUNG-A RETROSPECTIVE STUDY DONE ON LOBECTOMY SPECIMENS

To study the histolopathological spectrum of non-neoplastic lesions of lung and to evaluate in relation to age, gender and clinico-radiological findings. This study is done over a period of 1 year (Nov 2020 to Nov 2021) in the Department of Pathology, LNMC, Bhopal. Total of 33 lobectomy specimens were studied. Specimens were fixed in formalin and paraffin embedded H&E-stained tissue sections were studied. Special stains (Gomorri's methenamine silver stain and Periodic acid Schiff stain) were done where ever required. Non-neoplastic lesions from 3 (9.09%) women and 30 (90.90%) men, with a median age of 43.86 (Interquartile range: 23-60 years) were collected. Fibrotic interstitial changes comprised the most common category of histologic findings, noted in 20 (60.6%) patients. Most cases consisted of usual interstitial pneumonia (UIP) (30.30%), followed by smoking related interstitial fibrosis/SRIF (desquamative interstitial pneumonia like patterns and respiratory bronchiolitis like pattern) (12.12%), non-specific interstitial pneumonia (NSIP) (9.09%) and patterns of “undefined” fibrosis (6.06%) such as peribronchial fibrosis, organizing pneumonias and other patterns of fibrosis that did not fall into a recognized category of idiopathic interstitial pneumonia. Granulomatous pathology was identified in 4 (10.81%) patients. On chest X-ray/CT scan chest, majority of lung lesions presented as diffuse and patchy opacities with honeycombing and bronchiectasis. Cigarette smoking was associated with 4 lung lesions. Histopathologic classification plays an important role in separating variable forms of non-neoplastic lung lesions & further subcategorising idiopathic interstitial pneumonia into clinically meaningful categories have important differences in natural history, prognosis, and treatment

Comparative study of clinical and HRCT findings between idiopathic nonspecific interstitial pneumonia and connective tissue disease-associated nonspecific interstitial pneumonia / 实用医学杂志

Objective To investigate the difference in clinical features and chest HRCT findings between idiopathic nonspecific interstitial pneumonia(INSIP)and connective tissue disease-associated nonspecific interstitial pneumonia(CTD-NISP). Methods Totally 73 cases of NISP from 2011 to 2016 were retrospectively reviewed ,whose final diagnosis all were made after clinico-radiologic-pathologic discussion and 52 cases of them were diag-nosed as INSIP and 21 cases as CTD-NSIP. Clinical features ,lung function test results and chest HRCT findings of INSIP and CTD-NSIP were compared. Results Common underlying diseases of CTD-NSIP were poly-/dermato-myositis(PM/DM),rheumatoid arthritis(RA)and Sjogren syndrome(SS). The mean age of CTD-NSIP[(47.14 ± 9.24)y]was younger than that of INSIP[(59.09 ± 11.20)y](P<0.05). Compared to CTD-NSIP,expectoration was more common in patients with INSIP,while dry mouth/eyes,arthralgia and erythra were less common in INSIP (P < 0.05). Lung function test1 showed restrictive ventilatory dysfunction with dispersion function decline was found in both groups. There were no significant differences in lung function test results between INSIP and CTD-NSIP. In HRCT,the subpleural vertical line was more common in INSIP than that in CTD-NSIP,while patchy consolidation,subpleural curvilinear shadow,pleural effusion and esophageal dilation were less common in INSIP(P<0.05). Conclusions Specific difference of clinical and HRCT features between CTD-NSIP and INSIP are conducive to differentiating the two from each other.

Radiologic Approach to the Idiopathic Interstitial Pneumonias / 대한내과학회지

Idiopathic interstitial pneumonias (IIP), a heterogeneous group of diffuse parenchymal lung diseases, include seven clinicopathologic entities: idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), respiratory bronchiolitis (RB)-associated interstitial lung disease (ILD), desquamative interstitial pneumonia (DIP), and lymphoid interstitial pneumonia (LIP). Each of these entities has a typical histologic pattern that correlates well with imaging features. Thus, imaging plays an essential role in classifying and differentiating this group of diseases. The characteristic HRCT findings of IPF are reticular opacity with honeycombing and traction bronchiectasis in a predominantly basal and peripheral distribution. NSIP manifests as basal ground-glass opacity and reticular opacity. Honeycombing is rare. COP is characterized by patchy peripheral or peribronchovascular consolidation. AIP appears as extensive, mixed ground-glass opacity and consolidation. RB-ILD and DIP are smoking-related diseases associated with CT features of poorly defined centrilobular nodules and ground-glass opacity. LIP is a rare disease characterized by ground-glass opacity sometimes associated with perivascular cysts. Although some of idiopathic interstitial pneumonias may show diagnostic CT features, the final diagnosis of IIPs is usually made by means of evaluation of all the combined clinical, radiologic, and pathologic findings.

Clinical Significance of Serum Autoantibodies in Idiopathic Interstitial Pneumonia

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

Clinical Year in Review of Interstitial Lung Diseases: Focused on Idiopathic Interstitial Pneumonia / 결핵및호흡기질환

Interstitial lung disease (ILD) is a group of diseases characterized by pulmonary interstitial inflammation. Finally the inflammation results in pulmonary fibrosis and impairment of oxygen transportation. The causes of idiopathic interstitial pneumonia (IIP) are unknown. Diagnosis of IIP is not easy, especially distinguising between nonspecific interstitial pneumonia and usual interstitial pneumonia (UIP). First line treatments of IIP include corticosteroids and immune modulators, which have limited effect. Currently, several drugs are being researched to prevent and treat fibrosis. Newer drugs that may useful to treat pulmonary fibrosis include endothelin receptor antagonist, recombinant soluble TNF receptor antagonist, and cotrimoxazole. The causes of IIP are largely unknown, treatment is not specific, and prognosis is poor. Recent studies are underway to investigate the pathogenesis and treatment of IIP and pulmonary fibrosis. As the pathogenesis of IIP is elucidated, better treatments will emerge.

A Case of Nonspecific Interstitial Pneumonia Complicated with Spontaneous Pneumomediastinum, Subcutaneous Emphysema and Pneumatosis Interstinalis / 결핵및호흡기질환

Pneumatosis intestinalis or spontaneous pneumomediastinum are rarely associated with nonspecific interstitial pneumonia (NSIP). However, the development of both conditions in the same patient simultaneously has not been reported previously. A 56-year-old man with NSIP developed spontaneous pneumomediastinum accompanied by subcutaneous emphysema and pneumatosis intestinalis after the treatment with intravenous high dose steroid. The development of spontaneous pneumomediastinum, subcutaneous emphysema and pneumatosis intestinalis in this patient was possibly due to the factors such as NSIP, high dose steroid therapy and subclinical dermatomyositis. Treatment with corticosteroid and cyclosporin gradually improved his exacerbated NSIP and pneumomediastinum, subcutaneous emphysema, pneumatosis intestinalis.

HRCT Findings and Clinical Features in Non-specific and Usual Interstitial Pneumonia with Connective Tissue Diseases / 대한류마티스학회지

OBJECTIVE: The purpose of this study is to assess the clinical characteristics and the serial changes of high resolution CT (HRCT) findings and to correlate those with the results of clinical parameters in biopsy proven nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) with connective tissue diseases (CTD). METHODS: Retrospective analysis was made of forty patients with CTD diagnosed of NSIP and UIP from a single tertiary hospital between January 1996 and February 2006. RESULTS: UIP was common in rheumatoid arthritis, systemic sclerosis and Sjogren's syndrome, while NSIP was frequent in polymyositis/dermatomyositis. No significant difference was found in the clinical characteristics of patients with NSIP and UIP. In initial HRCT findings, extents of honeycombing and reticulation pattern were significantly more in UIP-CTD than in NSIP-CTD. In bronchoalveolar lavage (BAL) results, proportion of alveolar macrophages was significantly higher in NSIP-CTD than in UIP-CTD. In NSIP-CTD, significant increment in the extent of reticulation and honeycombing was noted in the serial HRCT findings despite the aggressive treatment. Significant correlation was found between leukocytosis and honeycombing change in NSIP-CTD. Despite no significant difference of survival between two groups, patients with UIP-CTD seem to have a higher mortality than those with NSIP-CTD. CONCLUSION: It is suggested that chest HRCT and BAL fluid analysis may be helpful in the differential diagnosis of NSIP- and UIP-CTD and leukocytosis in initial blood test might be predictive of honeycombing progression in NSIP-CTD. Further study will be required to compare with the prognosis of NSIP- and UIP-CTD.

A Case of Nonspecific Interstitial Pneumonia in a Patient with Ulcerative Colitis / 결핵및호흡기질환

Pulmonary complications of ulcerative colitis are relatively uncommon and may present as a variety of disorders. Ulcerative colitis-related interstitial lung disease is extremely rare. There are a few case reports of nonspecific interstitial pneumonia in ulcerative colitis worldwide but none in Korea. We report a patient with ulcerative colitis related biopsy-proven nonspecific interstitial pneumonia, who responded to prednisolone (1 mg/kg) and mesalazine therapy

Cyclophosphamide in the Treatment of Idiopathic UIP and NSIP / 결핵

BACKGROUND: Although corticosteroid and cytotoxic agent such as cyclophosphamide have been used for the treatment of idiopathic interstitial pneumonia (IIP), efficacy of these toxic drugs are unclear because previous reports included the patients who did not undergo surgical lung biopsy and none evaluated the response according to histopathologic entities of IIP. To answer this, we retrospectively analyzed the treatment response and side effects of corticosteroids and cyclophosphamide therapy in patients with idiopathic UIP and NSIP. METHODS: Among 61 patients with UIP and 26 patients with NSIP diagnosed by surgical lung biopsy at Samsung Medical Center from July 1996 to June 2002, those who received corticosteroid or cyclophosphamide therapy for at least 6 months and were followed for at least one year after the initiation of treatment were enrolled (32 UIP, 23 NSIP). Treatment response of 55 patients was assessed by ATS response criteria (clinical symptoms, pulmonary function test and radiological findings).Adverse reactions to either agent (42 cases of cyclophosphamide+/-low-dose prednisolone, 49 cases of prednisolone alone) were also analyzed. RESULTS: Irrespective of treatment regimen, NSIP showed more favorable response than UIP (6 months: 78.3% vs. 9.4%, 12 months: 69.6% vs. 9.4%, p<0.001). Cyclophosphamide showed comparable response to corticosteroid in NSIP while its efficacy was as poor as those of corticosteroid therapy in UIP. Significant adverse reaction to drug more frequently occurred in corticosteroid group (35.7%) than cyclophosphamide group (14.3%) (p=0.017). CONCLUSION: Cyclophosphamide is effective and more tolerable than corticosteroids in the treatment of idiopathic nonspecific interstitial pneumonia.

A Case of Nonspecific Interstitial Pneumonia in a Child

Interstitial pneumonia is a heterogenous group of inflammatory and fibrosing lesions that manifest themselves as infiltrative lung disease. Of these, nonspecific interstitial pneumonia is characterized as a variable degree of interstitial inflammation with or without fibrosis and is distinguished from usual interstitial pneumonia and desquamative interstitial pneumonia, histologically. The influx of inflammatory cells and the responses of immune effector cells injury to the alveolar wall and these initial injuries results in alveolitis and fibrosis. Consequently, the gas exchange throughout the alveolar wall is impaired and the patients suffer from lung diseases of a restrictive pattern. The chief complaints represented are dyspnea and dry cough. We experienced a case of nonspecific interstitial pneumonia in a 10-year old girl. The patient had been healthy and had not been exposed to organic dusts or other toxic materials. The pathology of lung biopsy tissue showed that the alveoli were thickened by a mixture of chronic inflammatory cells and collagen type fibrosis. High resolution computed tomography(HRCT) found the patchy areas of ground-glass opacity with patchy consolidation and irregular reticular opacity, and diffuse distribution without zonal predominance. The forced vital capicity(FVC) was 31%, forced expiratory volume in one second (FEV1) 29% and FEV1/FVC 90%, so a restrictive pulmonary insufficiency was found.

Clinical Features and Treatment Response in 18 Cases with Idiopathic Nonspecific Interstitial Pneumonia / 결핵

BACKGROUND: Nonspecific interstitial pneumonia (NSIP) has been reported recently to show much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating from UIP have not been defined clearly. METHOD: Among 120 patients with biopsy-proven diffuse interstitial lung diseases between July 1996 and March 2000 at Samsung Medical Center, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. RESULTS: 1) At diagnosis, 17 patients were female and average age was 55.2 +/-8.4 years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was 9.9+/-17.1 months. Increase in bronchoalveolar lavage fluid lymphocytes (23.0 +/-13.1%) was noted. On HRCT, ground glass and irregular linear opacity were seen but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients of whom medication was stopped in 3 patients due to severe side effects. Further medical therapy was impossible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascu lar necrosis of hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuous medication. 3) After medical treatment, 14 of 17 patients improved and 3 patients remained stable (mean w-up ; 24.1+/-11.2 months). FVC increased by 20.2 +/-11.2% of predicted value and the extent of ground glass opacity on HRCT decreased significantly (15.7+/-14.7%). 4) Of 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. CONCLUSION: Since idiopathic NSIP has unique clinical profiles and shows a good prognosis, differential diagnosis from UIP and aggressive medical treatment are needed.

Short-Term Efficacy of Steroid and Immunosuppressive Drugs in Patients with Idiopathic Pulmonary Fibrosis and Pre-treatment Factors Associated with Favorable Response / 결핵

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a diffuse inflammatory and fibrosing process that occurs within the interstitium and alveolus of the lung with invariably poor prognosis. The major problem in management of IPF results from the variable rate of disease progression and the difficulties in predicting the response to therapy. The purpose of this retrospective study was to evaluate the shortterm efficacy of steroid and immunosuppressive therapy for IPF and to identify the pre-treatment determinants of favorable response. METHOD: Twenty patients of IPF were included. Diagnosis of IPF was proven by thoracoscopic lung biopsy and they were presumed to have active progressive disease. The baseline evaluation in these patients included clinical history, pulmonary function test, bronchoalveolar lavage (BAL), and chest high resolution computed tomography (HRCT). Fourteen patients received oral prednisolone treatment with initial dose of 1mg/kg/day for 8 to 12 weeks and then tapering to low-dose prednis olone (0.5mg/kg/day). Six patients who previously had experienced significant side effects to steroid received 2mg/kg/day of oral cyclophosphamide with or without low-dose prednisolone. Follow-up evaluation was performed after 6 months of therapy. If patients met more than one of followings, they were considered to be responders: (1)improvement of more than one grade in dyspnea index, (2)improvement in FVC or TLC more than 10% or improvement in DLco more than 20% (3) decreased extent of disease in chest HRCT findings. RESULT: One patient died of extrapulmonary cause after 3 month of therapy, and another patient gave up any further medical therapy due to side effect of steroid. Eventually medical records of 18 patients were analyzed. Nine of 18 patients were classified into responders and the other nine patients into nonresponders. The histopathologic diagnosis of the responders were all nonspecific interstitial pneumonia (NSIP) and that of nonresponders were all usual interstitial pneumonia (UIP) (p<0.001). The other significant differences between the two groups were female predominance (p<0.01), smoking history (p<0.001), severe grade of dyspnea (p<0.05), lymphocytosis in BAL fluid (23.8+/-16.3% vs 7.83+/-3.6%, p < 0.05), and less honeycombing in chest HRCT findings (0% vs 9.22+/-2.3%, p < 0.001). CONCLUSION: Our results suggest that patients with histopathologic diagnosis of NSIP or lymphocytosis in BAL fluid are more likely to respond to steroid or immunosuppressive therapy. Clinical results in large numbers of IPF patients will be required to identify the independent variables.