The approach described below is an attempt to make order out of chaos for the pathologists dealing with diffuse lung disease and to provide radiologists some information about the histology of interstitial lung disease as it applies to HRCT. Obviously, the approach outlined is not applicable to all situations and many cases remain insoluble. Nevertheless, it does give the pathologist a framework within which interstitial lung disease can be assessed, and helps to develop a differential diagnosis histologically. The author thinks this approach also shows good correlation with many of the changes observed by the chest radiologist with HRCT of the lung. Recognizing an anatomic distribution may not necessarily be correlated with how a lesion is clinically viewed. For example, bronchiolocentricity is an important and prominent feature in hypersensitivity pneumonitis and respiratory bronchiolitis associated with interstitial lung disease, but neither is clinically considered an airway disease. The authors also make comments about transbronchial biopsy in opposition to open-lung biopsy in the pathologic assessment of difuse lung disease, although HRCT does provide information to the clinician to help select the most appropriate biopsy modality. Obviously, open-lung biopsy (and those retrieved by thoracoscopic techniques) offer more tissue and make it easier to observe anatomic distribution and reaction patterns. Nevertheless, transbronchial biopsies often include sufficient tissue (although fragmented) and the pathologist is able to mentally reconstruct the distribution and reaction pattern. Obviously, the changes assessed in transbronchial biopsy have to be individualized on a case-by-case basis, but it is surprising how often they are useful when carefully correlated with the clinical and radiological features in a given case.

Keywords: Pulmonary interstitial disorders. Pathology. Pulmonary fibrosis. Pulmonary biopsy.

Diffuse cystic lung diseases are characterized by cysts in more than one lung lobe, the cysts originating from various mechanisms, including the expansion of the distal airspaces due to airway obstruction, necrosis of the airway walls, and parenchymal destruction. The progression of these diseases is variable. One essential tool in the evaluation of these diseases is HRCT, because it improves the characterization of pulmonary cysts (including their distribution, size, and length) and the evaluation of the regularity of the cyst wall, as well as the identification of associated pulmonary and extrapulmonary lesions. When combined with clinical and laboratory findings, HRCT is often sufficient for the etiological definition of diffuse lung cysts, avoiding the need for lung biopsy. The differential diagnoses of diffuse cystic lung diseases are myriad, including neoplastic, inflammatory, and infectious etiologies. Pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, lymphocytic interstitial pneumonia, and follicular bronchiolitis are the most common diseases that produce this CT pattern. However, new diseases have been included as potential determinants of this pattern.

Keywords: Cysts; Diagnosis, differential; Lung diseases, interstitial; Tomography, X-ray computed.

Interstitial lung diseases (ILDs) in children constitute a heterogeneous group of rare diseases that have been described and classified according to experiences and research in adults. However, pediatric pulmonologists have observed that the clinical spectrum is broader in children than in adults, and that many of these disorders have different courses and treatment responses. In addition, probably due to the various stages of lung development and maturation, new clinical forms have been described, particularly in infants. This has broadened the classification of ILDs in this age bracket. The understanding that neither the usual definition nor the standard classification of these disorders entirely apply to children has prompted multicenter studies designed to increase knowledge of these disorders, as well as to standardize diagnostic and therapeutic strategies. We have reviewed the conceptualization of ILDs in children, taking into consideration the particularities of this group of patients when using the criteria for the classification of these diseases in adults. We have also made a historical review of several multicenter studies in order to further understanding of the problem. We have emphasized the differences in the clinical presentation, in an attempt to highlight knowledge of newly described entities in young children. We underscore the need to standardize management of laboratory and radiological routines, as well as of lung biopsy processing, taking such knowledge into account. It is important to bear in mind that, among the recently described disorders, genetic surfactant dysfunction, which is often classified as an idiopathic disease in adults, should be included in the differential diagnosis of ILDs.

Keywords: Lung diseases, interstitial; Lung diseases, interstitial/diagnosis; Lung diseases, interstitial/therapy; Child.

Background: Open lung biopsy is regarded as the gold standard for the diagnosis of diffuse pulmonary infiltrates. Objective: To determine the diagnostic yield, therapeutic changes, complications and mortality attributed to open lung biopsy in patients with diffuse pulmonary infiltrates and on mechanical ventilation. Method: We reviewed, retrospectively, the charts of 24 patients, ranging from 26 to 89 years of age, admitted to the intensive care units of two private hospitals and submitted to open lung biopsy. Results: Diagnostic positivity was found in 100% of patients, resulting in an alteration in the treatment regimen in 75%. Postoperative complications occurred in five patients (20.8%). There were no biopsy-related deaths, although global mortality was 45.8%. Conclusion: Open lung biopsy is a safe and high yield procedure for diagnosing diffuse pulmonary infiltrate in patients on mechanical ventilation. Despite the fact that no mortality impact factor has been assigned to such patients, data in the literature regarding prognosis must be taken into consideration.

Keywords: Biopsy. Respiratory insufficiency. Respiration artificial.

Macrolides are drugs that have antimicrobial effects, especially against intracellular pathogens. Various studies have shown that macrolides might also have anti-inflammatory effects. Macrolides inhibit the production of interleukins and can reduce pulmonary neutrophilic inflammation. Clinical trials have demonstrated beneficial effects of macrolides in various chronic lung diseases. The objective of this study was to review recent data in the medical literature on the anti-inflammatory effects of macrolides in childhood lung diseases by searching the Medline (PubMed) database. We used the following search terms: "macrolide and cystic fibrosis"; "macrolide and asthma"; "macrolide and bronchiolitis obliterans"; and "macrolide and acute bronchiolitis". We selected articles published in international scientific journals between 2001 and 2012. Clinical studies and in vitro evidence have confirmed the anti-inflammatory effect of macrolides in respiratory diseases. Some clinical trials have shown the benefits of the administration of macrolides in patients with cystic fibrosis, although the risk of bacterial resistance should be considered in the analysis of those benefits. Such benefits are controversial in other respiratory diseases, and the routine use of macrolides is not recommended. Further controlled clinical trials are required in order to assess the efficacy of macrolides as anti-inflammatory drugs, so that the benefits in the treatment of each specific clinical condition can be better established.

Keywords: Macrolides; Asthma; Cystic Fibrosis; Bronchiolitis.

Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (?2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

Keywords: Lung diseases, interstitial/epidemiology; Alveolitis, extrinsic allergic/epidemiology; Connective tissue diseases/epidemiology, Sarcoidosis/epidemiology; Idiopathic pulmonary fibrosis/epidemiology

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.

In lung function laboratories, statistical responses after bronchodilators (Bd) administration are widely used in patients with airflow limitation. However, their clinical relevance is debatable. Objective: To determine which spirometric parameters best reflect improvement in both exercise tolerance and exertional dyspnea in response to bronchodilators in obstructive lung diseases. Methods: Fifty patients with persistent asthma and/or COPD (FEV1/FVC = 41 ± 11%) were submitted to slow and forced vital capacity testing, MVV and a six-minute walking test (6 MW) following practice, before and after a 400 mg dose of salbutamol was given by MDI. Responses to Bd were expressed in absolute values and considered as increments to the initial values and predicted values. Responses to Bd were considered clinically significant if distance was longer than 30 m in the 6 MW test and/or if there was a 2-point decrease in the Borg scale in the walking distance. Results: 32 patients were responsive (R) to Bd and 18 were non-responsive (NR). As DMW correlated with age, (rs = -0.38 - p < 0.01) an analysis on spirometric data, including age as covariant, was performed and expressed as x ± SE. No difference in FEV1 was observed between the groups (R = 255 ± 57 ml; NR = 256 ± 43 ml). The same occurred regarding MVV (R = 11± 2 L/min; NR = 10 ± 2 L/min.). The best separation (p < 0.01) was given by changes in inspiration capacity (IC) followed by changes in slow vital capacity (SVC): IC% of initial R = 23 ± 3% and NR = 3 ± 4%; absolute IC = 411 ± 58 ml and NR = 163 ± 77 ml; predicted IC%: R = 19 ± 3% and NR = 3 ± 4%. For SVC, the values were: % initial - R = 18 ± 2% and NR = 9 ± 3%; absolute changes - R = 448 ± 52 ml and NR = 256 ± 70 ml. Increases in IC > 15% of the initial values and 0.3 L and increases in SVS > 15% of the initial values and 0.4 L determined responsive patients with positive predicted values as approximately 90%. Conclusion: Variations in FEV1, FVC and MVV do not predict improvement in exercise capacity after Bd. This is best reflected by 15% of increases in IC and/or in the SVC initial values.

Keywords: Obstructive lung diseases. Spirometry. Predictive value of tests. Bronchodilator agents. Exercise tolerance. Dyspnea.

Smoking is the leading cause of respiratory disease (RD). The harmful effects of smoking on the respiratory system begin in utero and influence immune responses throughout childhood and adult life. In comparison with "healthy" smokers, smokers with RD have peculiarities that can impede smoking cessation, such as a higher level of nicotine dependence; nicotine withdrawal; higher levels of exhaled carbon monoxide; low motivation and low self-efficacy; greater concern about weight gain; and a high prevalence of anxiety and depression. In addition, they require more intensive, prolonged treatment. It is always necessary to educate such individuals about the fact that quitting smoking is the only measure that will reduce the progression of RD and improve their quality of life, regardless of the duration and severity of the disease. Physicians should always offer smoking cessation treatment. Outpatient or inpatient smoking cessation treatment should be multidisciplinary, based on behavioral interventions and pharmacotherapy. It will thus be more effective and cost-effective, doubling the chances of success.

Keywords: Respiratory tract diseases/therapy; Respiratory tract diseases/drug therapy; Tobacco use disorder/epidemiology; Smoking cessation; Counseling; Lung neoplasms.

Objective: To determine the interobserver and intraobserver agreement in the diagnosis of interstitial lung diseases (ILDs) based on HRCT scans and the impact of observer expertise, clinical data and confidence level on such agreement. Methods: Two thoracic radiologists and two general radiologists independently reviewed the HRCT images of 58 patients with ILDs on two distinct occasions: prior to and after the clinical anamnesis. The radiologists selected up to three diagnostic hypotheses for each patient and defined the confidence level for these hypotheses. One of the thoracic and one of the general radiologists re-evaluated the same images up to three months after the first readings. In the coefficient analyses, the kappa statistic was used. Results: The thoracic and general radiologists, respectively, agreed on at least one diagnosis for each patient in 91.4% and 82.8% of the patients. The thoracic radiologists agreed on the most likely diagnosis in 48.3% (κ = 0.42) and 62.1% (κ = 0.58) of the cases, respectively, prior to and after the clinical anamnesis; likewise, the general radiologists agreed on the most likely diagnosis in 37.9% (κ = 0.32) and 36.2% (κ = 0.30) of the cases. For the thoracic radiologist, the intraobserver agreement on the most likely diagnosis was 0.73 and 0.63 prior to and after the clinical anamnesis, respectively. That for the general radiologist was 0.38 and 0.42.The thoracic radiologists presented almost perfect agreement for the diagnostic hypotheses defined with the high confidence level. Conclusions: Interobserver and intraobserver agreement in the diagnosis of ILDs based on HRCT scans ranged from fair to almost perfect and was influenced by radiologist expertise, clinical history and confidence level.

Keywords: Lung diseases, interstitial; Tomography, X-ray computed; Observer variation.

Objective: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method for the diagnosis and staging of lung disease, and its use is increasing worldwide. It has been used as a means of diagnosing lung cancer in its initial stages, and there are data supporting its use for the diagnosis of benign lung disease. The aim of this study was to share our experience with EBUS-TBNA and discuss its diagnostic value. Methods: We retrospectively analyzed the results related to 159 patients who underwent EBUS-TBNA at our pulmonary medicine clinic between 2010 and 2013. We recorded the location and size of lymph nodes seen during EBUS. Lymph nodes that appeared to be affected on EBUS were sampled at least twice. We recorded the diagnostic results of EBUS-TBNA and (for cases in which EBUS-TBNA yielded an inconclusive diagnosis) the final diagnoses after further investigation and follow-up. Results: We evaluated 159 patients, of whom 89 (56%) were male and 70 (44%) were female. The mean age was 54.6 ± 14.2 years among the male patients and 51.9 ± 11.3 years among the female patients. Of the 159 patients evaluated, 115 (84%) were correctly diagnosed by EBUS. The diagnostic accuracy of EBUS-TBNA was 83% for benign granulomatous diseases and 77% for malignant diseases. Conclusions: The diagnostic value of EBUS-TBNA is also high for benign pathologies, such as sarcoidosis and tuberculosis. In patients with mediastinal disorders, the use of EBUS-TBNA should be encouraged, primarily because it markedly reduces the need for mediastinoscopy.

Keywords: Sarcoidosis; Tuberculosis, pulmonary; Lung neoplasms; Bronchoscopy; Mediastinoscopy; Endosonography.

Many conditions result in chronic interstitial lung disease (ILD), being classified as fibrosing ILDs, including idiopathic pulmonary fibrosis, connective tissue diseases, sarcoidosis, and fibrotic hypersensitivity pneumonitis. HRCT plays an important role in the clinical evaluation of fibrosing ILDs. Current treatment perspectives are encouraging and reinforce the need for HRCT scans of adequate technical quality for early detection of fibrosing ILD. Despite efforts in this regard, the significance and management of imaging findings of early interstitial lung abnormalities have yet to be clarified. After identification of CT findings consistent with fibrosing ILD, radiologists must be able to identify characteristic morphological patterns and, in some cases, features of specific clinical entities. In cases in which HRCT features are not sufficiently specific for a definitive diagnosis, HRCT can aid in selecting the best site for surgical lung biopsy. CT follow-up is useful for identifying progressive fibrosing ILDs and detecting complications unrelated to the underlying disease, including infections, acute exacerbations, and neoplasms. Automated quantification tools have clinical applicability and are likely to be available for use in imaging analysis in the near future. In addition, incorporation of CT evaluation into scoring systems based on clinical and functional parameters for staging fibrosing disease is likely to become valuable in determining prognosis. Knowledge of the clinical applications of CT evaluation is essential for specialists managing patients with fibrosing ILD and can have a positive impact on the clinical course of the disease.

Keywords: Tomography, X-ray computed; Diagnostic imaging; Pulmonary fibrosis.