Objective: To evaluate the differences between surgical biopsies of distinct lung lobes in terms of the histopathological features of usual interstitial pneumonia, using a semiquantitative score. Methods: We selected all of the patients diagnosed with idiopathic pulmonary fibrosis and submitted to surgical biopsy in two distinct lobes between 1995 and 2005 at the Hospital São Paulo and other hospitals operated by the Federal University of São Paulo. In the histological evaluation of the specimens, we used a semiquantitative method based on previous studies, assigning a score to each of the biopsied sites. Results: In this sample of patients, we found no statistically significant differences that would alter the stage of the disease, based on the score used. This finding was independent of the biopsy site (middle lobe or lingular segment). Conclusions: No significant histological differences were found between the lung lobes studied. The definitive histological diagnosis of usual interstitial pneumonia did not alter the stage of the disease.

Keywords: Lung diseases, interstitial; Pulmonary fibrosis; Thoracic surgery; Pathology; Thoracic surgery, ­video-assisted.

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a progressive interstitia pulmonary disease of unknown etiology. Since Hamman's and Rich's (1944) reports, many studies have tried to find a histological marker for the correlation between prognosis and response to therapy. However, there are many doubts regarding pathogenesis. In addition, it is generally accepted that response to therapy is related to the relative degree of cellularity and fibrosis. The purpose of this study is to describe the results of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, using a semi-quantitative method by independent evaluation of two pathologists, in 24 open lung biopsies with the diagnosis of idiopathic pulmonary fibrosis. Fourteen histological features were analyzed using the 0 to 5 scale for interstitial alterations and the 0 to 2 scale for the airway changes. There was significant interobserver agreement for all histological features with Kw (Kappa) variations between 0.47 and 0.92. There was significant disagreement only for septal inflammatory intensity analysis, suggesting that these features must be discussed by the pathologists. The semi-quantitative method assessment was effective.

Keywords: Idiopathic pulmonary fibrosis (IPF). Usual interstitial pneumonia (UIP). Semi-quantitative method assessment.

Objective: To correlate semiquantitative evaluation of intrapulmonary vascular dilatations (IPVD) with quantitative evaluation of shunt levels, as well as to describe clinical and pulmonary function findings in a sample of liver disease patients with IPVD. Methods: Patients presenting transthoracic echocardiography (TTE) positivity for IPVD underwent clinical evaluation, pulmonary function tests and pulmonary shunt quantification (scintigraphy with technetium-99m-labeled macroaggregated albumin and blood gas analysis after pure oxygen breathing). Results: A total of 28 liver cirrhosis patients were studied (mean age, 47.5 years; 60.7% were Child-Pugh class B). A 4-point, ascending scale was used as a measure of IPVD intensity, which was scored as 1, 2, 3 and 4, respectively, in 13 (46.4%), 9 (32.1%), 2 (7.1%) and 4 (14.3%) of the patients. Patients were divided into a low-intensity group (scores 1 and 2) and a high-intensity group (scores 3 and 4). The mean shunt assessed using scintigraphy was 14.9% in the sample as a whole and was lower in the low-intensity group (11.7% vs. 26.3%; p = 0.01). The mean shunt by blood gas analysis was higher in the high-intensity group (8.3% vs. 16.3%; p < 0.001). Mean PaO2 was lower in the high-intensity group. There was a negative correlation between DLCO and IPVD severity (r = −0.406, p = 0.01). Conclusions: TTE is a safe, useful tool for assessing IPVD severity in liver disease patients. The IPVD intensity assessed using TTE correlated with the intrapulmonary shunt values obtained through the quantitative methods evaluated, as well as with pulmonary gas exchange abnormalities.

Keywords: Anoxia; Liver cirrhosis; Hepatopulmonary syndrome; Echocardiography.

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.

Objective: To describe demographic characteristics, surgical results, postoperative complications, and overall survival rates in surgically treated patients with lung metastases. Methods: This was a retrospective analysis of 119 patients who underwent a total of 154 lung metastasis resections between 1997 and 2011. Results: Among the 119 patients, 68 (57.1%) were male and 108 (90.8%) were White. The median age was 52 years (range, 15-75 years). In this sample, 63 patients (52.9%) presented with comorbidities, the most common being systemic arterial hypertension (69.8%) and diabetes (19.0%). Primary colorectal tumors (47.9%) and musculoskeletal tumors (21.8%) were the main sites of origin of the metastases. Approximately 24% of the patients underwent more than one resection of the lesions, and 71% had adjuvant treatment prior to metastasectomy. The rate of lung metastasis recurrence was 19.3%, and the median disease-free interval was 23 months. The main surgical access used was thoracotomy (78%), and the most common approach was wedge resection with segmentectomy (51%). The rate of postoperative complications was 22%, and perioperative mortality was 1.9%. The overall survival rates at 12, 36, 60, and 120 months were 96%, 77%, 56%, and 39%, respectively. A Cox analysis confirmed that complications within the first 30 postoperative days were associated with poor prognosis (hazard ratio = 1.81; 95% CI: 1.09-3.06; p = 0.02). Conclusions: Surgical treatment of lung metastases is safe and effective, with good overall survival, especially in patients with fewer metastases.

Keywords: Neoplasm metastasis; Survival analysis; Thoracic surgery; Metastasectomy.

Objective: To retrospectively analyze the medical charts of patients with pulmonary malformations submitted to surgical treatment and to investigate the clinical evolution prior to the definitive diagnosis. Methods: We analyzed the medical charts of patients with pulmonary malformations operated on at the São Paulo Hospital-Federal University of São Paulo/Paulista School of Medicine-from 1969 to 2004. Each medical chart was analyzed as to the following aspects: clinical profile; diagnosis; previous treatment; surgical treatment; and nosocomial complications. The inclusion criteria were having received a diagnosis of pulmonary malformation, having undergone pulmonary resection, and chart data being complete. Results: The analysis of the medical charts revealed that 60 patients diagnosed with pulmonary malformations-27 cases of bronchogenic cyst, 14 cases of congenital lobar emphysema, 10 cases of pulmonary sequestration, and 9 cases of cystic adenomatoid malformation-underwent surgery. Ages ranged from 4 days to 62 years (mean, 17.9 years). There was a predominance of males (55%). Ninety-two percent of the patients presented symptoms (mean duration, 15.37 months). Of the 60 patients undergoing surgery, 27 (45%) received preoperative home or hospital treatment with antibiotics. Regarding complications, we observed that morbidity was 23%, and mortality was 3.3%. Surgical times ranged from 1 to 8 h (mean, 3.2 h). Conclusions: Misdiagnosis or delayed diagnosis of pulmonary malformations resulted in unnecessary treatments and hospitalizations, as well as in frequent, recurrent infectious complications. We believe that the definitive treatment is surgery, which is curative and has low morbidity and mortality rates.

Keywords: Bronchogenic cyst; Bronchopulmonary sequestration; Cystic adenomatoid malformation of lung, congenital; Respiratory tract infections; Thoracic surgery.

We report the case of a 56-year-old patient who underwent left single lung transplantation for idiopathic pulmonary fibrosis (IPF). Despite the high level of immunosuppression after the surgery, there was rapid progression to IPF in the native (right) lung as demonstrated by thoracoscopic lung biopsy. After 104 days on mechanical ventilation, the patient underwent right lung transplant and was discharged from the hospital on postoperative day 26.

Keywords: Idiopathic pulmonary fibrosis; Lung transplantation; Case reports [publication type].

Objective: To determine the main congenital lung malformations treated and the principal diagnostic methods employed, as well as the indications for surgical treatment and the results obtained, at a referral facility for pediatric thoracic surgery. Methods: We reviewed the medical charts of 52 patients anatomopathologically diagnosed with congenital lung malformations and who had been submitted to pulmonary resection between January of 1997 and December of 2006. Exclusion criteria were age ≥ 12 years and incomplete clinical data. The final sample comprised 35 patients. Results: In this sample, the mean age was 31 months, and there was a predominance of males (n = 21). The anatomopathological findings were cystic adenomatoid malformation (n = 14), congenital lobar emphysema (n = 13), pulmonary sequestration (n = 8) and arteriovenous malformation (n = 1). The most common type of lung resection was left lower lobectomy (in 25.71%) followed by different types of segmentectomy (in 22.85%), left upper lobectomy (in 22.85%), right upper lobectomy (in 14.28%), right lower lobectomy (in 8.57%) and middle lobectomy (in 5.71%). Of the 35 patients, 34 (97.14%) were submitted to closed pleural drainage, with a mean duration of thoracic drainage of 3.9 days. Ten patients (28.5%) presented with postoperative complications. There were no deaths in our sample. Conclusions: Pulmonary resection for the treatment of congenital lung malformations is a safe procedure, presenting low morbidity and no mortality at a referral facility for pediatric thoracic surgery.

Keywords: Cystic adenomatoid malformation of lung, congenital; Bronchopulmonary sequestration; Pneumonectomy; Pulmonary surgical procedures; Pulmonary emphysema.

The objective of this study was to analyze the outcome of surgical treatment of pulmonary aspergilloma. To that end, we evaluated 14 adult patients so treated between 1981 and 2009 at the Botucatu School of Medicine University Hospital, in the city of Botucatu, Brazil. Data were collected from the medical records of the patients. Ten patients (71%) presented with simple pulmonary aspergilloma, and 4 (29%) presented with complex pulmonary aspergilloma. Hemoptysis was the most common symptom, and tuberculosis was the most prevalent preexisting lung disease. Two patients (14%) underwent surgery on more than one occasion. There were no intraoperative deaths. Half of the patients developed postoperative complications, prolonged air leak and empyema being the most common.

Keywords: Pulmonary aspergillosis; Tuberculosis, pulmonary; Thoracic surgery.

Necrotizing pneumonia is a serious complication of lobar pneumonia. Four children aged between ten months and three years were admitted with acute bacteremic pneumonia and developed sepsis, pleural effusion, and respiratory distress despite adequate antibiotic treatment and chest tube drainage. Decortication and pulmonary resection were performed in all of them. The observed complications were bronchopleural fistula and one death. The emergency pulmonary resection is indicated when pulmonary necrosis is associated to sepsis and massive bronchopleural fistula. In such circumstances, morbidity and mortality are higher than in other conditions.

Keywords: staphylococcal pneumonia; thoracotomy; lung, surgery

Objective: To correlate tomographic findings with pulmonary function parameters in patients with idiopathic pulmonary fibrosis (IPF). Methods: A cross-sectional study was carried out, in which 30 nonsmoking patients with IPF were evaluated. Using a semiquantitative scoring system, the following high-resolution computerized tomography (HRCT) findings were quantified: total interstitial disease (TID), reticular abnormality/honeycombing, and ground-glass opacity (GGO). The functional variables were measured by spirometry, forced oscillation technique (FOT), helium dilution method, as well as the single-breath method of measuring diffusion capacity of the lung for carbon monoxide (DLCO). Results: Of the 30 patients studied, 18 were female, and 12 were male, with a mean age of 70.9 years. We found that TID and reticular abnormality and honeycombing correlated significantly (negative correlations) with the measurements of forced vital capacity (FVC), total lung capacity (TLC), DLCO, and dynamic respiratory compliance were found, as well as that GGO correlated significantly (and positively) with residual volume/TLC. The ratio of forced expiratory flow between 25 and 75% of FVC to FVC (FEF25-75%/FVC) correlated positively with TID, reticular abnormality/honeycombing, and GGO. Conclusion: In IPF patients, the measurements of volume, diffusion, and dynamic compliance are the physiological variables which best reflect the extent of the interstitial disease on HRCT scans.

Keywords: Lung diseases, interstitial; Pulmonary fibrosis; Tomography, X-ray computed; Respiratory function tests.

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: Bone disease is a common comorbidity in patients with cystic fibrosis (CF). We sought to determine risk factors and identify potential biochemical markers for CF-related bone disease (CFBD) in a unique cohort of CF patients with end-stage lung disease undergoing lung transplantation (LTx) evaluation. Methods: All of the CF patients who were evaluated for LTx at our center between November of 1992 and December of 2010 were included in the study. Clinical data and biochemical markers of bone turnover, as well as bone mineral density (BMD) at the lumbar spine and femoral neck, were evaluated. Spearman's rho and multivariate logistic regression analysis were used. Results: A total of 102 adult CF patients were evaluated. The mean age was 28.1 years (95% CI: 26.7-29.5), and the mean body mass index was 17.5 kg/m2 (95% CI: 17.2-18.2). Mean T-scores were −2.3 and −1.9 at the lumbar spine and femoral neck, respectively, being lower in males than in females (−2.7 vs. −2.0 at the lumbar spine and −2.2 vs. −1.7 at the femoral neck). Overall, 52% had a T-score of < −2.5 at either skeletal site. The homozygous Phe508del genotype was found in 57% of patients without osteoporosis and in 60% of those with low BMD. Mean T-scores were not particularly low in patients with severe CFTR mutations. Although the BMI correlated with T-scores at the femoral neck and lumbar spine, serum 25-hydroxyvitamin D and parathyroid hormone levels did not. Conclusions: CFBD is common in CF patients with end-stage lung disease, particularly in males and patients with a low BMI. It appears that CF mutation status does not correlate with CFBD. In addition, it appears that low BMD does not correlate with other risk factors or biochemical parameters. The prevalence of CFBD appears to have recently decreased, most likely reflecting increased efforts at earlier diagnosis and treatment.

Keywords: Lung transplantation; Cystic fibrosis; Bone density; Osteoporosis.

Objective: To describe the results of the surgical treatment of children with necrotizing pneumonia. Methods: A retrospective analysis of the medical charts of 20 children diagnosed with necrotizing pneumonia and submitted to surgical treatment between March of 1997 and September of 2008 in the thoracic surgery departments of two hospitals in the city of Manaus, Brazil. We compiled data regarding age, gender, etiologic agent, indications for surgery, type of surgical resection performed, and postoperative complications. Results: The mean age of the patients was 30 months. Of the 20 patients studied, 12 (60%) were female. The most common etiologic agents were Staphylococcus aureus, in 5 patients (25%), and Klebsiella sp., in 2 (10%). The indications for surgery were sepsis, in 16 patients (80%), and bronchopleural fistula, in 4 (20%). The types of surgical procedures performed were lobectomy, in 12 patients (60%), segmentectomy, in 7 (35%), and bilobectomy, in 1 (5%). There were 8 patients (40%) who also underwent decortication. The postoperative complications were as follows: bronchopleural fistula, in 4 patients (20%); empyema, in 1 (5%); pneumatocele, in 1 (5%); and phlebitis of the left arm, in 1 (5%). Four (20%) of the patients died. Conclusions: Surgical resection should be considered in patients with evidence of pulmonary necrosis. Resection is indicated in cases of severe sepsis, high output bronchopleural fistula, or acute respiratory failure that are refractory to clinical treatment.

Keywords: Pneumonia; Necrosis; Lung abscess; Empyema, pleural.

Objective: To compare FEV1 and FVC, calculated using three sets of reference equations (devised by Polgar & Promadhat, Hsu et al. and Mallozi in 1971, 1979 and 1995, respectively), and to determine whether the three are similar in predicting lung function in children and adolescents with distinct body mass indices (BMIs). Methods: The individuals were separated into four groups in accordance with the reference standards of the National Center for Health Statistics: underweight (UW), normal weight (NW), overweight (OW), and obese (OB). All were then submitted to spirometry. Results: We evaluated 122 healthy children and adolescents, aged 7-14 years. The FVC values predicted for NW females and UW males through the use of the Hsu et al. equation were significantly higher than the measured values, as were the FEV1 values for UW females and males predicted via the Polgar & Promadhat and Hsu et al. equations. In NW females, the FEV1 values predicted via the Polgar & Promadhat equation were significantly higher than were the measured values. Conclusions: In individuals with distinct BMIs, the measured FVC and FEV1 values were not equivalent to those predicted via the Polgar & Promadhat and Hsu et al. equations. The same was not true for the Mallozi equations. The BMI was not a relevant factor for the predictive index of these equations; therefore, the Mallozi equations can be used without alteration for children and adolescents with distinct BMIs.

Keywords: Spirometry; Reference values; Body mass index; Child; Adolescent.

Objectives: To examine the relationship between chronic bacterial infection and pulmonary hypertension, using Doppler echocardiography, in patients with cystic fibrosis (CF). Methods: A prospective cross-sectional study involving CF patients (≥ 16 years of age) admitted to a program for adults with the disease. The study included 40 patients with a mean age of 23.7 ± 6.3 years. Patients were submitted to clinical evaluation, Doppler echocardiography, pulmonary function tests, chest X-rays and sputum cultures of Pseudomonas aeruginosa and Burkholderia cepacia. Results: In terms of the following variables, no significant differences were found between P. aeruginosapositive patients and P. aeruginosa-negative patients: clinical score (p = 0.472); forced expiratory volume in one second (FEV1; p = 0.693); radiological score (p = 0.760); tricuspid regurgitant jet velocity (TRV, p = 0.330); diameter of the right ventricle (DRV, p = 0.191); and right ventricular/pulmonary artery (RV/PA) systolic acceleration time (SAT, p = 0.330). B. cepacia-positive patients presented significantly lower FEV1 than did B. cepacia-negative patients (p = 0.011). No significant differences were found between B. cepacia-positive patients and B. cepacia-negative patients regarding the following variables: clinical score (p = 0.080); radiological score (p = 0.760); TRV (p = 0.613); DRV (p = 0.429); and RV/PA SAT (p = 0.149). Conclusions: Chronic infection with P. aeruginosa or B. cepacia presented no association with pulmonary hypertension in adult CF patients. Pulmonary function was worse in B. cepacia-positive patients than in P. aeruginosa-positive patients.

Keywords: Cystic fibrosis; Bacterial infections; Hypertension, pulmonary; Echocardiography, Doppler.

Objective: To determine the prevalence of gastroesophageal reflux disease (GERD) and to evaluate its clinical presentation, as well as the esophageal function profile in patients with idiopathic pulmonary fibrosis (IPF). Methods: In this prospective study, 28 consecutive patients with IPF underwent stationary esophageal manometry, 24-h esophageal pH-metry and pulmonary function tests. All patients also completed a symptom and quality of life in GERD questionnaire. Results: In the study sample, the prevalence of GERD was 35.7%. The patients were then divided into two groups: GERD+ (abnormal pH-metry; n = 10) and GERD− (normal pH-metry; n = 18). In the GERD+ group, 77.7% of the patients presented at least one typical GERD symptom. The pH-metry results showed that 8 (80%) of the GERD+ group patients had abnormal supine reflux, and that the reflux was exclusively in the supine position in 5 (50%). In the GERD+ and GERD− groups, respectively, 5 (50.0%) and 7 (38.8%) of the patients presented a hypotensive lower esophageal sphincter, 7 (70.0%) and 10 (55.5%), respectively, presenting lower esophageal dysmotility. There were no significant differences between the groups regarding demographic characteristics, pulmonary function, clinical presentation or manometric findings. Conclusions: The prevalence of GERD in the patients with IPF was high. However, the clinical and functional characteristics did not differ between the patients with GERD and those without.

Keywords: Pulmonary fibrosis; Gastroesophageal reflux; Prevalence; Manometry; Esophageal pH monitoring.

Objetivo: Analisar as características funcionais pulmonares, a resposta farmacodinâmica a um broncodilatador e sua prescrição em pacientes com diagnóstico de fibrose cística (FC). Métodos: Estudo de coorte retrospectivo de pacientes (6-18 anos) com diagnóstico de FC acompanhados em um centro de referência, capazes de realizar testes de função pulmonar (TFP) entre 2008 e 2010. Foram analisados CVF, VEF1 e FEF25-75%, em percentual do previsto, antes e após prova broncodilatadora (pré-BD e pós-BD, respectivamente) de 312 TFP. Foram realizadas ANOVA para medidas repetidas e comparações múltiplas. Resultados: Foram incluídos no estudo 56 pacientes. Desses, 37 e 19, respectivamente, tinham resultados de TFP entre 2008 e 2010 e apenas em 2009-2010, formando dois grupos. No grupo com TFP nos três anos estudados, houve redução significativa em VEF1 pós-BD em 2008-2010 (p = 0,028) e 2009-2010 (p = 0,036) e em FEF25-75% pré-BD e pós-BD em todas as comparações múltiplas (2008 vs. 2009; 2008 vs. 2010; e 2009 vs. 2010). No grupo com TFP apenas em 2009-2010, não houve diferenças significativas em nenhuma das comparações das variáveis estudadas. Dos 312 TFP, somente 24 (7,7%) apresentaram resposta significativa ao broncodilatador e pertenciam a pacientes sem prescrição de broncodilatador durante o período estudado. Conclusões: Houve perda funcional, com indicação de doença pulmonar progressiva, nos pacientes com FC estudados. Houve maiores alterações no FEF25-75%, sugerindo o comprometimento inicial de vias aéreas menores.

Keywords: Fibrose cística; Testes de função respiratória; Broncodilatadores.

Objective: Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods: Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results: The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion: In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Keywords: Drug tolerance; Expanded access program; Interstitial lung disease; Tyrosine kinase inhibitor.