Objective: To investigate the relationship between the timed "up and go" (TUG) test and physical activity in daily life (PADL) in patients with interstitial lung disease (ILD) and propose a cutoff point to identify physically inactive individuals. Methods: Participants performed the TUG test at a usual pace (TUGusual) and at a fast pace (TUGfast). Exercise capacity was assessed by the six-minute walk test, lung function was assessed by whole-body plethysmography, quadriceps strength was assessed by maximal voluntary isometric contraction, and PADL was assessed by an activity monitor worn for six consecutive days. PADL variables included number of steps/day, time spent/day in activities of different intensities, and time spent/day in different postures. A ROC curve was plotted to identify physically inactive individuals on the basis of daily steps (5,000 steps/day) and moderate to vigorous physical activity (MVPA; 30 min/day). Results: Fifty-three ILD patients (26 women, with a mean age of 60 ± 11 years) were included in the study. TUGusual and TUGfast correlated moderately with the number of steps/day and time spent/day in light physical activity and MVPA (-0.60 < r < -0.41; p < 0.05 for all). ROC curves for TUGusual showed that the cutoffs of = 9.25 s and = 7.9 s can identify physically inactive individuals on the basis of 5,000 steps/day (AUC: 0.73; sensitivity, 76%; specificity, 70%) and 30 min/day of MVPA (AUC: 0.85; sensitivity, 90%; specificity, 75%). Participants who performed worse on TUGusual (i.e., = 9.25 s) showed lower peripheral muscle strength, exercise capacity, and PADL. Conclusions: Performance on TUGusual and TUGfast correlates moderately with PADL in patients with ILD. A TUGusual performance = 9.25 s appears to be able to identify physically inactive individuals in this population.

Keywords: Physical functional performance; Lung diseases, interstitial; Activities of daily living.

High-resolution computed tomography (HRCT) is the radiological imaging technique best suited to revealing changes in lung structure. Various HRCT findings, taken together, can represent typical patterns. These patterns, in conjunction with the anatomical distribution of findings and with clinical data, can narrow the differential diagnosis of diffuse interstitial lung disease and, in many cases, indicate the correct diagnosis with a high degree of accuracy. The most common HRCT patterns seen in cases of diffuse interstitial lung diseases are the nodular pattern, linear/reticular opacities, cystic lesions, ground-glass opacities and consolidations. This article reviews the correlations between HRCT patterns and pathologic findings, summarizing the most common causes, as well as detailing the methods of investigation employed in order to diagnose the most common types of chronic diffuse lung disease.

Keywords: Lung diseases, interstitial/pathology; Tomography, X-Ray computed; Diagnostic techniques, respiratory system.

Objective: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). Methods: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). Results: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. Conclusions: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

Keywords: Idiopathic interstitial pneumonias; Autoantibodies; Connective tissue diseases; Autoimmunity.

In patients with myositis, the lung is commonly involved, and the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies marks the presence or predicts the development of interstitial lung disease (ILD). A distinct clinical entity-antisynthetase syndrome-is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud's phenomenon, and mechanic's hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable.

Keywords: Lung diseases, interstitial; Pneumonia; Infection.

Objective: To determine predictors of health-related quality of life (HRQoL) in patients with interstitial lung disease (ILD). Methods: A cross-sectional study comprising 63 patients, all of whom underwent lung function testing and the six-minute walk test. The following instruments were used: the Medical Outcomes Study 36-item Short-form Survey (SF-36), the Saint George's Respiratory Questionnaire (SGRQ), the Beck Anxiety Inventory, the Beck Depression Inventory, and the Modified Medical Research Council Dyspnea Scale. Principal component analysis was used in order to reduce the dimensionality of the data, thereby identifying the predictor variables, and multiple linear regression analysis was used in order to identify the explanatory variables. Results: Of the 63 patients, 34 were female. The mean age was 60.1 ± 13.3 years, the mean FVC was 64.17 ± 15.54% of predicted, and the mean DLCO was 44.21 ± 14.47% of predicted. All of the patients evaluated had impaired HRQoL, scoring worst for the SF-36 physical functioning and SGRQ activity domains. Of the patients evaluated, 60.3% and 57.1% showed symptoms of anxiety and depression, respectively. The principal component analysis identified one predictor of physical HRQoL and one predictor of mental HRQoL. Depression had a strong influence on the predictor of mental HRQoL, and the degree of dyspnea had a strong influence on both predictors of HRQoL in the patients evaluated. Variables related to lung function, exercise capacity, and anxiety had no impact on these predictors. Conclusions: In our sample of patients with ILD, the degree of dyspnea had a major impact on the physical and mental HRQoL, and depression had an impact on mental HRQoL.

Keywords: Anxiety; Depression; Dyspnea; Lung diseases, interstitial; Quality of life; Respiratory function tests.

Respiratory bronchiolitis-associated interstitial lung disease is one of many within the spectrum of smoking-related diffuse infiltrative lung diseases. The clinical and functional characteristics are typically subtle. Herein, we describe two cases of diagnosed through open-lung biopsy, and characterized by insidious evolution of dyspnea, digital clubbing, cystic lesions on computed tomography scans, and hipoxemia upon exertion. We emphasize that, when smokers are evaluated, it is imprtant to consider a diagnosis of respiratory bronchiolitis-associated interstitial lung disease in the context of interstitial cystitis, as well as in that of lymphangioleiomyomatosis, eosinophilic granuloma and idiophatic pulmonary fibrosis.

Keywords: Smoking. Interstitial lung diseases. Bronchiolitis.

Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.

Keywords: Alveolitis, extrinsic allergic; Idiopathic pulmonary fibrosis; Lung diseases, interstitial; Connective tissue diseases.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Keywords: Lung diseases, interstitial; Collagen diseases; Scleroderma, systemic; Arthritis, rheumatoid; Myositis; Therapeutics.

The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild or benign symptoms of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.

Keywords: Idiopathic interstitial pneumonias; Autoantibodies; Connective tissue diseases; Autoimmune diseases; Diagnosis, differential.

Objective: To study the clinical, radiological, and histopathological patterns of transbronchial biopsy (TBB) used in order to confirm the diagnosis in patients with clinical suspicion of interstitial lung disease (ILD) treated at a tertiary-care university hospital. Methods: We reviewed the medical records, radiology reports, and reports of transbronchial biopsies from all patients with suspected ILD who underwent TBB between January of 1999 and December of 2006 at the Hospital das Clínicas de Botucatu, located in the city of Botucatu, Brazil. Results: The study included 56 patients. Of those, 11 (19.6%) had a definitive diagnosis of idiopathic pulmonary fibrosis (IPF), the rate of which was significantly higher in the patients in which ILD was a possible diagnosis in comparison with those in which ILD was the prime suspect (p = 0.011), demonstrating the contribution of TBB to the diagnostic confirmation of these diseases. The histopathological examination of the biopsies revealed that 27.3% of the patients with IPF showed a pattern of organizing pneumonia, which suggests greater disease severity. The most common histological pattern was the indeterminate pattern, reflecting the peripheral characteristic of IPF. However, the fibrosis pattern showed high specificity and high negative predictive value. For CT scan patterns suggestive of IPF, the ROC curve showed that the best relationship between sensitivity and specificity occurred when five radiological alterations were present. Honeycombing was found to be strongly suggestive of IPF (p = 0.01). Conclusions: For ILDs, chest CT should always be performed, and TBB should be used in specific situations, according to the suspicion and distribution of lesions.

Keywords: Lung diseases, interstitial; Diagnosis, differential; Bronchoscopy.

Objective: To estimate the frequency of interstitial lung disease in a group of patients with progressive systemic sclerosis, and to describe the clinical, functional and radiological characteristics of the patients studied. Methods: Fifty-eight patients diagnosed with progressive systemic sclerosis were submitted to high-resolution computed tomography of the chest, pulmonary function tests and a blood test for anti-Scl 70 antibodies. Comparisons were drawn between patients with interstitial lung disease and those without. Logistic regression with multivariate analysis was used to identify factors predictive of interstitial lung disease. Results: Of the 58 patients evaluated, 51.7% presented interstitial lung disease on high-resolution computerized tomography scans. Dyspnea and cough were the most common symptoms (seen in 65.5% and 39.7%, respectively). Bronchiolectasis and honeycombing were the most common tomographic abnormalities (observed in 83.3% and 80%, respectively). When compared to individuals without interstitial lung disease, patients with the condition had a comparable frequency of pulmonary and extrapulmonary symptoms but presented progressive systemic sclerosis of longer duration, a higher frequency of crackling rales, higher rates of anti-Scl 70 positivity, lower vital capacity and reduced total lung capacity. Only forced vital capacity < 80% was found to be a predictor of interstitial lung disease. Conclusion: Interstitial lung disease was common in this group of patients with progressive systemic sclerosis. No correlation with symptoms was found, although interstitial lung disease was found to correlate with crackling rales and with anti-Scl 70 positivity. Nevertheless, only reduced forced vital capacity was found to be predictive of interstitial lung disease.

The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD.

Keywords: Lung diseases, interstitial; Arthritis, rheumatoid; Antirheumatic agents; Antibodies, monoclonal, humanized/adverse effects.

Objective: To characterize the prevalence of latent tuberculosis infection (LTBI) in patients with interstitial lung diseases (ILDs) requiring immunosuppression. Only 5 to 10% of individuals infected with Mycobacterium tuberculosis develop tuberculosis, and certain groups of patients have an increased risk of illness, such as the immunocompromised. Patients with ILDs are frequently treated with immunosuppressants and, therefore, might have a higher risk of developing the disease. Methods: Prospective study conducted at the ILD reference center of the Federal University of Paraná from January 2019 to December 2020. The screening of LTBI was performed with the use of the tuberculin skin test (TST). Results: The sample consisted of 88 patients, of whom 64.8% were women, with a mean age of 61.4 years. The most frequent diagnoses were autoimmune rheumatic disease ILD (38.6%) and hypersensitivity pneumonitis (35.2%). The most common immunosuppressant in use at the time of the TST was prednisone, either in combination with mycophenolate (19.3%) or alone (17.1%). The majority of participants had fibrotic lung disease, characterized by a reticular interstitial pattern on chest computed tomography (79.5%) and moderate to severe functional impairment (mean FVC 69.2%). A prevalence of LTBI of 9.1% (CI 95%, 2.1%-15.1%) was found, with a TST median of 13. Conclusion: Patients with ILD who are treated with immunosuppressants are not commonly screened for LTBI, despite being under a greater risk of progression to active disease. This study suggests the need for a more cautious approach to these patients.

Keywords: Latent tuberculosis infection; Interstitial lung diseases; Immunosuppression; Tuberculin test.