Objective: To investigate the applicability of ultrasound imaging of the diaphragm in interstitial lung disease (ILD). Methods: Using ultrasound, we compared ILD patients and healthy volunteers (controls) in terms of diaphragmatic mobility during quiet and deep breathing; diaphragm thickness at functional residual capacity (FRC) and at total lung capacity (TLC); and the thickening fraction (TF, proportional diaphragm thickening from FRC to TLC). We also evaluated correlations between diaphragmatic dysfunction and lung function variables. Results: Between the ILD patients (n = 40) and the controls (n = 16), mean diaphragmatic mobility was comparable during quiet breathing, although it was significantly lower in the patients during deep breathing (4.5 ± 1.7 cm vs. 7.6 ± 1.4 cm; p < 0.01). The patients showed greater diaphragm thickness at FRC (p = 0.05), although, due to lower diaphragm thickness at TLC, they also showed a lower TF (p < 0.01). The FVC as a percentage of the predicted value (FVC%) correlated with diaphragmatic mobility (r = 0.73; p < 0.01), and an FVC% cut-off value of < 60% presented high sensitivity (92%) and specificity (81%) for indentifying decreased diaphragmatic mobility. Conclusions: Using ultrasound, we were able to show that diaphragmatic mobility and the TF were lower in ILD patients than in healthy controls, despite the greater diaphragm thickness at FRC in the former. Diaphragmatic mobility correlated with ILD functional severity, and an FVC% cut-off value of < 60% was found to be highly accurate for indentifying diaphragmatic dysfunction on ultrasound.

Keywords: Diaphragm/ultrasonography; Lung diseases, interstitial; Respiratory muscles; Respiratory function tests.

Objective: To translate the King's Brief Interstitial Lung Disease (K-BILD) questionnaire to Portuguese and culturally adapt it for use in Brazil. The K-BILD quantifies the health status of patients with ILD. Methods: The process involved the following steps: authorization from the author of the original (English-language) questionnaire; translation of the questionnaire to Portuguese by three translators, working independently; merging of the translations by a committee of specialists; back-translation of the questionnaire to English; revision and readjustment of the back-translation by the committee of specialists; evaluation by the original author; revision of the back-translation; cognitive debriefing (verification of the clarity and acceptability of the Portuguese-language version in the target population-i.e., patients with ILD); and finalization of the Portuguese-language version. Results: In the cognitive debriefing step, 20 patients with ILD were interviewed. After the interviews, the clarity and acceptability index of each question was ≥ 0.8, which is considered acceptable. Conclusions: The Portuguese-language version of K-BILD appears to be easily administered to and understood by patients with ILD in Brazil. To our knowledge, this is the only instrument in Brazilian Portuguese that is designed to evaluate the impact that ILD has on the various aspects of the lives of those it affects.

Keywords: Lung diseases, interstitial; Pulmonary fibrosis; Surveys and questionnaires.

O diafragma é o principal músculo da respiração e age de forma contínua e ininterrupta para mantê-la. Muitas patologias podem causar disfunção diafragmática, que é geralmente subdiagnosticada na prática clínica em virtude de sua apresentação inespecífica. Embora várias técnicas tenham sido usadas na avaliação da função diafragmática, o diagnóstico de disfunção diafragmática ainda é problemático. A ultrassonografia diafragmática ganhou importância em virtude de suas muitas vantagens: não é invasiva, não expõe os pacientes à radiação, está amplamente disponível, fornece resultados imediatos, é altamente precisa e é repetível à beira do leito. Vários autores descreveram técnicas ultrassonográficas para avaliar a excursão e o espessamento diafragmático na zona de aposição. Estudos recentes propuseram a padronização dos métodos. Este artigo de revisão analisa a utilidade da ultrassonografia na avaliação da função diafragmática, abordando os detalhes da técnica, os principais achados e as aplicações clínicas.

Keywords: Ultrassonografia; Diafragma/diagnóstico por imagem; Músculos respiratórios; Estado terminal; Doenças respiratórias; Doenças neuromusculares.

Objective: To assess, using ultrasound, the effects that changes in body position have on diaphragmatic mobility in healthy subjects during spontaneous breathing. Methods: The study involved seven healthy female volunteers, all of whom were nonsmokers, well nourished, and free of any cardiopulmonary disease. They were submitted to pulmonary function testing and ultrasound evaluation of the mobility of the right diaphragm by the craniocaudal displacement of the left branch of the portal vein using an ultrasound device in mode B. The mobility of the right diaphragm was evaluated in right decubitus and in left decubitus. The order of evaluation was previously determined in a random drawing. Results: The average mobility of the right diaphragm in right decubitus (51.30 ± 9.69 mm) was significantly higher (p = 0.03) than that observed in left decubitus (45.93 ± 10.37 mm). Conclusion: The results suggest that, during spontaneous ventilation, the dependent portion of the diaphragm presents greater mobility than does the nondependent portion, and that the technique used was sufficiently sensitive to detect variations in diaphragmatic mobility related to changes in posture.

Keywords: Diaphragm; Ultrasonography; Respiratory function tests; Posture.

Objective: To compare pre-extubation physiological characteristics and ultrasound variables between patients intubated for COVID-19 compared to a clinical population and those intubated for other reasons. Methods: This was a secondary analysis of a prospective cohort study of patients undergoing invasive mechanical ventilation (IMV) for more than 48 h. Patients were divided into two groups: those intubated for COVID-19-induced ARDS and those intubated for other clinical reasons. Ultrasound assessment of lung and diaphragm function was performed before extubation. The results were compared between the two groups of patients. Results: In comparison with the patients without COVID-19, those with the disease were younger (a median age of 58 [46-76] years vs. a median age of 75 [69-85] years; p = 0.01), had fewer comorbidities (a median Charlson Comorbidity Index of 2 [1-4] vs. a median Charlson Comorbidity Index of 5 [4-6]; p < 0.01), and were less severely ill at admission (a median APACHE II score of 9 [8-14] vs. a median APACHE II score of 18 [13-22]; p < 0.01). In addition, the median duration of IMV was longer in the COVID-19 patients (11 [9-23] days vs. 6 [3-8] days; p < 0.01). Although extubation success rates were similar between the COVID-19 and non-COVID-19 groups (22 [71%] vs. 35 [77.8%]), median lung ultrasound score differed between the two groups (23 [18-25] vs. 15 [11-18]; p < 0.01), as did median diaphragmatic excursion (2.1 [1.7-2.4] vs. 1.7 [1.2-2.0]; p < 0.01). Conclusions: Although patients with COVID-19 requiring ventilatory support are younger and have fewer comorbidities than those intubated for other clinical reasons, they experience longer hospital stays. Although lung ultrasound score can differ between patients with and without COVID-19, these differences do not significantly translate into extubation success rates. Therefore, the utility of ultrasound scores in weaning COVID-19 patients from IMV needs further study.

Keywords: COVID-19; Ventilator weaning; Diaphragm; Ultrasound/diagnosis; Lung.

Objective: To evaluate the impact of lipoabdominoplasty on diaphragmatic mobility (DM) and lung function in healthy women. Methods: This was a prospective cohort study using high-resolution ultrasound and forced spirometry to assess DM and lung function, respectively, prior to lipoabdominoplasty, as well as on postoperative day (POD) 10 and POD 30. DM was measured under two conditions: during tidal volume breathing and during a VC maneuver. Results: The sample consisted of 20 women, with a mean age of 39.85 ± 7.52 years and a mean body mass index of 26.21 ± 2.0 kg/m2. Comparing the preoperative and postoperative periods, we found that DM and lung function values were significantly lower after lipoabdominoplasty, the mean DM on POD 10 being 17% and 15% lower during tidal volume breathing and during the VC maneuver, respectively, in comparison with the preoperative mean (p = 0.009 and p < 0.001, respectively). In addition, FEV1, FVC, and PEF were significantly lower on POD 10 than in the preoperative period (p = 0.046, p = 0.002, and p < 0.001, respectively), returning to preoperative values by POD 30. Conclusions: Lipoabdominoplasty appears to have negative short-term repercussions for DM and lung function in healthy women. However, lung function and DM are both apparently restored to preoperative conditions by POD 30. (ClinicalTrials.gov identifier: NCT02762526 [http://www.clinicaltrials.gov/])

Keywords: Abdominoplasty; Lipectomy; Ultrasonography; Diaphragm/physiology; Diaphragm/physiopathology; Lung/physiology; Lung/physiopathology; Respiratory mechanics; Spirometry; Respiratory function tests.

Objective: To evaluate diaphragmatic mobility in relation to lung function, respiratory muscle strength, dyspnea, and physical activity in daily life (PADL) in patients with COPD. Methods: We included 25 patients with COPD, classified according to the Global Initiative for Chronic Obstructive Lung Disease criteria, and 25 healthy individuals. For all of the participants, the following were evaluated: anthropometric variables, spirometric parameters, respiratory muscle strength, diaphragmatic mobility (by X-ray), PADL, and the perception of dyspnea. Results: In the COPD group, diaphragmatic mobility was found to correlate with lung function variables, inspiratory muscle strength, and the perception of dyspnea, whereas it did not correlate with expiratory muscle strength or PADL. Conclusions: In patients with COPD, diaphragmatic mobility seems to be associated with airway obstruction and lung hyperinflation, as well as with ventilatory capacity and the perception of dyspnea, although not with PADL.

Keywords: Pulmonary disease, chronic obstructive; Diaphragm; Spirometry; Dyspnea; Maximal respiratory pressures.

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.

Lung cancer is the leading cause of cancer-related deaths worldwide. Promising new therapies have recently emerged from the development of molecular targeted drugs; particularly promising are those blocking the signal transduction machinery of cancer cells. One of the most widely studied cell signaling pathways is that of EGFR, which leads to uncontrolled cell proliferation, increased cell angiogenesis, and greater cell invasiveness. Activating mutations in the EGFR gene (deletions in exon 19 and mutation L858R in exon 21), first described in 2004, have been detected in approximately 10% of all non-squamous non-small cell lung cancer (NSCLC) patients in Western countries and are the most important predictors of a response to EGFR tyrosine-kinase inhibitors (EGFR-TKIs). Studies of the EGFR-TKIs gefitinib, erlotinib, and afatinib, in comparison with platinum-based regimens, as first-line treatments in chemotherapy-naïve patients have shown that the EGFR-TKIs produce gains in progression-free survival and overall response rates, although only in patients whose tumors harbor activating mutations in the EGFR gene. Clinical trials have also shown EGFR-TKIs to be effective as second- and third-line therapies in advanced NSCLC. Here, we review the main aspects of EGFR pathway activation in NSCLC, underscore the importance of correctly identifying activating mutations in the EGFR gene, and discuss the main outcomes of EGFR-TKI treatment in NSCLC.

Keywords: Molecular targeted therapy; Receptor, epidermal growth factor; Lung neoplasms/drug therapy; Mutation; Oncogenes.

Objective: To investigate the concurrent validity, as well as the intra- and inter-rater reliability, of assessing diaphragmatic mobility by area (DMarea) on chest X-rays of healthy adults. Methods: We evaluated anthropometric parameters, pulmonary function, and diaphragmatic mobility in 43 participants. Two observers (rater A and rater B) determined diaphragmatic mobility at two time points. We used Pearson's correlation coefficient to evaluate the correlation between DMarea and the assessment of diaphragmatic mobility by distance (DMdist). To evaluate intra- and inter-rater reliability, we used the intraclass correlation coefficient (ICC [2,1]), 95% CI, and Bland-Altman analysis. Results: A significant correlation was found between the DMarea and DMdist methods (r = 0.743; p < 0.0001). For DMarea, the intra-rater reliability was found to be quite high for the right hemidiaphragm (RHD)-ICC (2,1) = 0.92 (95% CI: 0.86-0.95) for rater A and ICC (2,1) = 0.90 (95% CI: 0.84-0.94) for rater B-and the left hemidiaphragm (LHD)-ICC (2,1) = 0.96 (95% CI: 0.93-0.97) for rater A and ICC (2,1) = 0.91 (95% CI: 0.81-0.95) for rater B-(p < 0.0001 for all). Also for DMarea, the inter-rater reliability was found to be quite high for the first and second evaluations of the RHD-ICC (2,1) = 0.99 (95% CI: 0.98-0.99) and ICC (2,1) = 0.95 (95% CI: 0.86-0.97), respectively-and the LHD-ICC (2,1) = 0.99 (95% CI: 0.98-0.99) and ICC (2,1) = 0.94 (95% CI: 0.87-0.97)-(p < 0.0001 for both). The Bland-Altman analysis showed good agreement between the mobility of the RHD and that of the LHD. Conclusions: The DMarea method proved to be a valid, reliable measure of diaphragmatic mobility.

Keywords: Diaphragm/physiology; Validation studies; Reproducibility of results; Radiography.

Objective: To compare diaphragmatic mobility, lung function, and respiratory muscle strength between COPD patients with and without thoracic hyperkyphosis; to determine the relationship of thoracic kyphosis angle with diaphragmatic mobility, lung function, and respiratory muscle strength in COPD patients; and to compare diaphragmatic mobility and thoracic kyphosis between male and female patients with COPD. Methods: Participants underwent anthropometry, spirometry, thoracic kyphosis measurement, and evaluation of diaphragmatic mobility. Results: A total of 34 patients with COPD participated in the study. Diaphragmatic mobility was significantly lower in the group of COPD patients with thoracic hyperkyphosis than in that of those without it (p = 0.002). There were no statistically significant differences between the two groups of COPD patients regarding lung function or respiratory muscle strength variables. There was a significant negative correlation between thoracic kyphosis angle and diaphragmatic mobility (r = −0.47; p = 0.005). In the sample as a whole, there were statistically significant differences between males and females regarding body weight (p = 0.011), height (p < 0.001), and thoracic kyphosis angle (p = 0.036); however, there were no significant differences in diaphragmatic mobility between males and females (p = 0.210). Conclusions: Diaphragmatic mobility is lower in COPD patients with thoracic hyperkyphosis than in those without it. There is a negative correlation between thoracic kyphosis angle and diaphragmatic mobility. In comparison with male patients with COPD, female patients with COPD have a significantly increased thoracic kyphosis angle.

Keywords: Pulmonary disease, chronic obstructive; Kyphosis; Diaphragm.