Clinical, tomographic and functional comparison of sporadic and tuberous sclerosis complex-associated forms of lymphangioleiomyomatosis: a retrospective cohort study.

Background: Lymphangioleiomyomatosis (LAM) is a rare disease that can occur sporadically (S-LAM) or associated with the tuberous sclerosis complex (TSC-LAM). The natural history of LAM is not completely understood, including whether there is a difference between the clinical courses of the two forms. This study aimed to compare the clinical, functional and tomographic features between S-LAM and TSC-LAM, and evaluate the annual rates of change in lung function. Methods: This retrospective cohort study included patients with LAM followed up between 1994 and 2019. Clinical, functional and imaging variables were evaluated, and the lung cysts were automatically quantified. Quality of life and predictors of lung function impairment were accessed, and the annual rate of lung function decline was compared between S-LAM and TSC-LAM. Results: Of the 107 patients included, 77 had S-LAM and 30 had TSC-LAM. Although patients with TSC-LAM had a higher prevalence of renal angiomyolipomas and neurological and dermatological manifestations, pulmonary function tests were similar. Patients with S-LAM had a greater rate of forced expiratory volume in 1 s decline and a higher extent of cysts. Pneumothorax, desaturation in the 6-minute walking test and a higher extent of lung cysts were predictors of functional impairment. A greater impact on vitality and emotional health was observed in the TSC-LAM. Conclusion: Greater functional decline and a higher cystic extension were found in patients with S-LAM. Our study provides a broad clinical, functional and tomographic characterisation of patients with LAM, adding valuable information to the existing evidence to better understand the two forms of the disease.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging.

Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

Lung cancer screening in Brazil: recommendations from the Brazilian Society of Thoracic Surgery, Brazilian Thoracic Association, and Brazilian College of Radiology and Diagnostic Imaging / Recomendações da Sociedade Brasileira de Cirurgia Torácica, Sociedade Brasileira de Pneumologia e Tisiologia e Colégio Brasileiro de Radiologia e Diagnóstico por Imagem para o rastreamento do câncer de pulmão no Brasil

ABSTRACT Although lung cancer (LC) is one of the most common and lethal tumors, only 15% of patients are diagnosed at an early stage. Smoking is still responsible for more than 85% of cases. Lung cancer screening (LCS) with low-dose CT (LDCT) reduces LC-related mortality by 20%, and that reduction reaches 38% when LCS by LDCT is combined with smoking cessation. In the last decade, a number of countries have adopted population-based LCS as a public health recommendation. Albeit still incipient, discussion on this topic in Brazil is becoming increasingly broad and necessary. With the aim of increasing knowledge and stimulating debate on LCS, the Brazilian Society of Thoracic Surgery, the Brazilian Thoracic Association, and the Brazilian College of Radiology and Diagnostic Imaging convened a panel of experts to prepare recommendations for LCS in Brazil. The recommendations presented here were based on a narrative review of the literature, with an emphasis on large population-based studies, systematic reviews, and the recommendations of international guidelines, and were developed after extensive discussion by the panel of experts. The following topics were reviewed: reasons for screening; general considerations about smoking; epidemiology of LC; eligibility criteria; incidental findings; granulomatous lesions; probabilistic models; minimum requirements for LDCT; volumetric acquisition; risks of screening; minimum structure and role of the multidisciplinary team; practice according to the Lung CT Screening Reporting and Data System; costs versus benefits of screening; and future perspectives for LCS.

RESUMO O câncer de pulmão (CP) é uma das neoplasias mais comuns e letais no Brasil, e apenas 15% dos pacientes são diagnosticados nos estágios iniciais. O tabagismo persiste como o responsável por mais de 85% de todos os casos. O rastreamento do CP (RCP) por meio da TC de baixa dosagem de radiação (TCBD) reduz a mortalidade do CP em 20%, e, quando combinado com a cessação do tabagismo, essa redução chega a 38%. Na última década, diversos países adotaram o RCP como recomendação de saúde populacional. No Brasil, embora ainda incipiente, a discussão sobre o tema é cada vez mais ampla e necessária. Com o intuito de aumentar o conhecimento e estimular o debate sobre o RCP, a Sociedade Brasileira de Cirurgia Torácica, a Sociedade Brasileira de Pneumologia e Tisiologia e o Colégio Brasileiro de Radiologia e Diagnóstico por Imagem constituíram um painel de especialistas para elaborar as recomendações para o RCP. As recomendações aqui apresentadas foram baseadas em revisão narrativa da literatura, com ênfase em grandes estudos populacionais, em revisões sistemáticas e em recomendações de diretrizes internacionais, sendo construídas após ampla discussão pelo grupo de especialistas. Os temas revisados foram os seguintes: porque rastrear, considerações gerais sobre tabagismo, epidemiologia do CP, critérios de elegibilidade, achados incidentais, lesões granulomatosas, modelos probabilísticos, requisitos mínimos da TCBD, aquisições volumétricas, riscos do rastreamento, estrutura mínima e papel da equipe multidisciplinar, conduta segundo o Lung CT Screening Reporting and Data System (Lung-RADS), custos vs. benefícios e perspectivas do rastreamento.

Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19.

OBJECTIVE: The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. METHODS: The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. RESULTS: A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. CONCLUSION: Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

Complications of lung transplantation on computed tomography: pictorial essay.

Lung transplantation is becoming increasingly more common as an alternative treatment for end-stage lung disease. Despite advances in laboratory testing, surgical technique, and donor/recipient selection, lung transplantation is still associated with significant mortality, due to postoperative complications. This paper consists of a brief review of postoperative complications in lung transplant recipients, illustrating those complications with computed tomography images.

Transplantes pulmonares são procedimentos progressivamente mais realizados em todo o mundo como opção para tratamento de doenças pulmonares em estágio terminal. Apesar dos avanços laboratoriais, da técnica cirúrgica e da seleção de doadores e receptores, a mortalidade nesses procedimentos ainda é significativa, em razão de complicações típicas dos pacientes transplantados. Este trabalho consiste em uma revisão da literatura acerca do tema, ilustrando as complicações abordadas por meio de imagens de tomografia computadorizada.

Complicações dos transplantes pulmonares na tomografia computadorizada: ensaio iconográfico / Complications of lung transplantation on computed tomography: pictorial essay

Resumo Transplantes pulmonares são procedimentos progressivamente mais realizados em todo o mundo como opção para tratamento de doenças pulmonares em estágio terminal. Apesar dos avanços laboratoriais, da técnica cirúrgica e da seleção de doadores e receptores, a mortalidade nesses procedimentos ainda é significativa, em razão de complicações típicas dos pacientes transplantados. Este trabalho consiste em uma revisão da literatura acerca do tema, ilustrando as complicações abordadas por meio de imagens de tomografia computadorizada.

Abstract Lung transplantation is becoming increasingly more common as an alternative treatment for end-stage lung disease. Despite advances in laboratory testing, surgical technique, and donor/recipient selection, lung transplantation is still associated with significant mortality, due to postoperative complications. This paper consists of a brief review of postoperative complications in lung transplant recipients, illustrating those complications with computed tomography images.

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

BACKGROUND: Coronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity. METHODS: A prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion. RESULTS: In total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01). CONCLUSION: ICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission.

Correlation between chest computed tomography findings and pulmonary function test results in the post-recovery phase of COVID-19

ABSTRACT Objective The radiological and functional lung sequelae in COVID-19 survivors remain unclear. We compared the chest computed tomography findings of COVID-19 patients with normal and abnormal pulmonary function test results in the post-recovery phase. Methods The data of consecutive patients who underwent pulmonary function tests and chest computed tomography within 14 days after recovery from COVID-19 at two medical centers between May and October 2020 were collected retrospectively. Two thoracic radiologists who were blinded to the clinical information and pulmonary function test results classified the patients according to the computed tomography features, evidence of fibrotic-like changes, and semi-quantitative quantification of the extent of pulmonary abnormalities. The clinical characteristics and computed tomography findings of patients with normal pulmonary function test results were compared with those of patients with abnormal results. Results A total of 101 COVID-19 survivors, comprising 48 ambulatory and 53 hospitalized patients, were included at a median of 95 days from initial symptom onset. Computed tomography revealed fibrotic-like changes in 10.9% of patients. A reduction in the diffusion capacity of carbon monoxide was the most common lung function abnormality (19.8%). Abnormal diffusion capacity of carbon monoxide was associated with the presence and extension of lung opacities on chest computed tomography scans and fibrotic pulmonary abnormalities. The sensitivity, specificity, and accuracy of reduced diffusion capacity of carbon monoxide for detecting fibrotic-like pulmonary changes on chest computed tomography scans were 72.7%, 87.8%, and 86.1%, respectively. Conclusion Our study suggests that the presence of an abnormal diffusion capacity of carbon monoxide in the post-recovery phase of COVID-19 is associated with a greater risk of long-term parenchymal lung disease, as evidenced by the presence of fibrotic-like changes on chest computed tomography scans, such as traction bronchiectasis and architectural distortion.

COVID-19 pneumonia assessed at a private hospital, a field hospital, and a public-referral hospital: population analysis, chest computed tomography findings, and outcomes.

Objective: To compare a private quaternary referral hospital, a public tertiary hospital, and a field hospital dedicated to patients with COVID-19, regarding patients' characteristics, clinical parameters, laboratory, imaging findings, and outcomes of patients with confirmed diagnosis of COVID-19. Methods: Retrospective multicenter observational study that assessed the association of clinical, laboratory and CT data of 453 patients with COVID-19, and also their outcomes (hospital discharge or admission, intensive care unit admission, need for mechanical ventilation, and mortality caused by COVID-19). Results: The mean age of patients was 55 years (±16 years), 58.1% of them were male, and 41.9% were female. Considering stratification by the hospital of care, significant differences were observed in the dyspnea, fever, cough, hypertension, diabetes mellitus parameters, and CT score (p < 0.05). Significant differences were observed in ward admission rates, with a lower rate in the private hospital (40.0%), followed by the public hospital (74.1%), and a higher rate in the field hospital (89.4%). Regarding intensive care unit admission, there was a higher rate in the public hospital (25.2%), followed by the private hospital (15.5%), and a lower rate in the field hospital (9.9%). In the analysis of the discharge and death outcomes, it was found that there was a higher number of patients discharged from the private hospital (94.2%), compared to the field hospital (90.1%) and public hospital (82.3%) and a higher number of deaths in the public hospital (17.7%) compared to the private hospital and field hospital (5.8 and 0% respectively). Conclusion: The analysis of the data regarding the population treated with COVID-19 during the first wave in different levels of care in the public and private health systems in the city of São Paulo revealed statistically significant differences between the populations, reflecting distinct outcomes.

Chronic lung lesions in COVID-19 survivors: predictive clinical model.

OBJECTIVE: This study aimed to propose a simple, accessible and low-cost predictive clinical model to detect lung lesions due to COVID-19 infection. DESIGN: This prospective cohort study included COVID-19 survivors hospitalised between 30 March 2020 and 31 August 2020 followed-up 6 months after hospital discharge. The pulmonary function was assessed using the modified Medical Research Council (mMRC) dyspnoea scale, oximetry (SpO2), spirometry (forced vital capacity (FVC)) and chest X-ray (CXR) during an in-person consultation. Patients with abnormalities in at least one of these parameters underwent chest CT. mMRC scale, SpO2, FVC and CXR findings were used to build a machine learning model for lung lesion detection on CT. SETTING: A tertiary hospital in Sao Paulo, Brazil. PARTICIPANTS: 749 eligible RT-PCR-confirmed SARS-CoV-2-infected patients aged ≥18 years. PRIMARY OUTCOME MEASURE: A predictive clinical model for lung lesion detection on chest CT. RESULTS: There were 470 patients (63%) that had at least one sign of pulmonary involvement and were eligible for CT. Almost half of them (48%) had significant pulmonary abnormalities, including ground-glass opacities, parenchymal bands, reticulation, traction bronchiectasis and architectural distortion. The machine learning model, including the results of 257 patients with complete data on mMRC, SpO2, FVC, CXR and CT, accurately detected pulmonary lesions by the joint data of CXR, mMRC scale, SpO2 and FVC (sensitivity, 0.85±0.08; specificity, 0.70±0.06; F1-score, 0.79±0.06 and area under the curve, 0.80±0.07). CONCLUSION: A predictive clinical model based on CXR, mMRC, oximetry and spirometry data can accurately screen patients with lung lesions after SARS-CoV-2 infection. Given that these examinations are highly accessible and low cost, this protocol can be automated and implemented in different countries for early detection of COVID-19 sequelae.

Prognostic factors of worse outcome for hospitalized COVID-19 patients, with emphasis on chest computed tomography data: a retrospective study.

OBJECTIVE: To evaluate anthropometric and clinical data, muscle mass, subcutaneous fat, spine bone mineral density, extent of acute pulmonary disease related to COVID-19, quantification of pulmonary emphysema, coronary calcium, and hepatic steatosis using chest computed tomography of hospitalized patients with confirmed diagnosis of COVID-19 pneumonia and verify its association with disease severity. METHODS: A total of 123 adults hospitalized due to COVID-19 pneumonia were enrolled in the present study, which evaluated the anthropometric, clinical and chest computed tomography data (pectoral and paravertebral muscle area and density, subcutaneous fat, thoracic vertebral bodies density, degree of pulmonary involvement by disease, coronary calcium quantification, liver attenuation measurement) and their association with poorer prognosis characterized through a combined outcome of intubation and mechanical ventilation, need of intensive care unit, and death. RESULTS: Age (p=0.013), body mass index (p=0.009), lymphopenia (p=0.034), and degree of pulmonary involvement of COVID-19 pneumonia (p<0.001) were associated with poor prognosis. Extent of pulmonary involvement by COVID-19 pneumonia had an odds ratio of 1,329 for a poor prognosis and a cutoff value of 6.5 for increased risk, with a sensitivity of 64.9% and specificity of 67.1%. CONCLUSION: The present study found an association of high body mass index, older age, extent of pulmonary involvement by COVID-19, and lymphopenia with severity of COVID-19 pneumonia in hospitalized patients.

Challenges of Implementing Lung Cancer Screening in a Developing Country: Results of the Second Brazilian Early Lung Cancer Screening Trial (BRELT2).

PURPOSE: This paper aims to present the results of a series of several Brazilian institutions that have been carrying out lung cancer screening (LCS). MATERIALS AND METHODS: This is a retrospective, cohort study, with follow-up of individuals of both sexes, with a heavy smoking history, who participated in LCS programs between December 2013 and January 2021 in six Brazilian institutions located in the states of São Paulo, Rio Grande do Sul, and Bahia. RESULTS: Three thousand four hundred seventy individuals were included, of which 59.8% were male (n = 2,074) and 50.6% were current smokers (n = 1,758), with 60.7 years (standard deviation 8.8 years). Lung-RADS 4 was observed in 233 (6.7%) patients. Biopsy was indicated by minimally invasive methods in 122 patients (3.5%). Two patients who demonstrated false-negative biopsies and lung cancer were diagnosed in follow-up. Diagnosis of lung cancer was observed in 74 patients (prevalence rate of 2.1%), with 52 (70.3%) in stage I or II. Granulomatous disease was found in 20 patients. There were no statistical differences in the incidence of lung cancer, biopsies, granulomatous disease, and Lung-RADS 4 nodules between public and private patients. CONCLUSION: There are still many challenges and obstacles in the implementation of LCS in developing countries; however, our multi-institutional data were possible to obtain satisfactory results in these scenarios and to achieve similar results to the main international studies. Granulomatous diseases did not increase the number of lung biopsies. The authors hope that it could stimulate the creation of organized screening programs in regions still endemic for tuberculosis and other granulomatous diseases.

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

A Convolutional Neural Network Approach to Quantify Lung Disease Progression in Patients with Fibrotic Hypersensitivity Pneumonitis (HP).

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p<0.001). On CNN classification, increased extent of fibrosis and consolidation were the measures most strongly correlated with FVC decline (r2=0.54 and r2=0.44, p<0.001). Conclusion CT histogram and CNN measurements provide sensitive measures of functional changes in fibrotic HP patients over time. Increased fibrosis was associated with FVC decline, providing index of disease progression. CNN may help improve fibrotic HP follow-up, providing a sensitive tool for progressive interstitial changes, which can potentially contribute to clinical decisions for individualizing disease management.