Every year, a large number of individuals become dependent on mechanical ventilation because of a loss of diaphragm function. The most common causes are cervical spinal trauma and neuromuscular diseases. We have developed an experimental model to evaluate the performance of electrical stimulation of the diaphragm in rabbits using single-channel electrodes implanted directly into the muscle. Various current intensities (10, 16, 20, and 26 mA) produced tidal volumes above the baseline value, showing that this model is effective for the study of diaphragm performance at different levels of electrical stimulation.

Keywords: Rabbits; Diaphragm; Electric stimulation; Models, animal.

Objective: Although various strategies have been proposed for eradicating Pseudomonas aeruginosa in patients with cystic fibrosis (CF), only a few employ multistep treatment in children colonized by that pathogen for the first time. The aim of this study was to describe the effectiveness of a three-phase eradication protocol, initiated after the first isolation of P. aeruginosa, in children with CF in Brazil. Methods: This was a retrospective real-life study in which we reviewed the medical records of pediatric CF patients in whom the eradication protocol was applied between June of 2004 and December of 2012. The three-phase protocol was guided by positive cultures for P. aeruginosa in airway secretions, and the treatment consisted of inhaled colistimethate and oral ciprofloxacin. Success rates were assessed after each phase, as well as cumulatively. Results: During the study period, 47 episodes of P. aeruginosa colonization, in 29 patients, were eligible for eradication. Among the 29 patients, the median age was 2.7 years, 17 (59%) were male, and 19 (65%) had at least one F508del allele. All 29 patients completed the first phase of the protocol, whereas only 12 and 6 completed the second and third phases, respectively. Success rates for eradication in the three treatment phases were 58.6% (95% CI: 40.7-74.5), 50.0% (95% CI: 25.4-74.6), and 66.7% (95% CI: 30.0-90.3), respectively. The cumulative success rate was 93.1% (95% CI: 78.0-98.1). Treatment failure in all three phases occurred in only 2 patients. Conclusions: In this sample of patients, the multistep eradication protocol was effective and had a high success rate.

Keywords: Cystic fibrosis/therapy; Cystic fibrosis/prevention & control; Pseudomonas aeruginosa; Treatment outcome.

Objective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

Keywords: Lung neoplasms; Chemotherapy, adjuvant; Cisplatin/toxicity; Vinorelbine/toxicity.

We report the case of a child with tetraplegia after cervical trauma, who subsequently underwent diaphragmatic pacemaker implantation. We reviewed the major indications for diaphragmatic pacing and the types of devices employed. We highlight the unequivocal benefit of diaphragmatic pacing in the social and educational reintegration of individuals with tetraplegia.

Keywords: Spinal cord injuries; Respiration, artificial; Pacemaker, artificial; Quadriplegia.

We aimed to test a new model of self-expanding tracheal stent so that it might be made available for clinical use. Using direct laryngoscopy, we placed polyurethane-coated, nitinol stents into the middle third of the trachea in 25 New Zealand rabbits. After a mean observation period of 26 days, we evaluated stent migration, degree of expansion, attachment, adherence, formation of granulation tissue, presence of inflammatory infiltrate, parietal involvement, and epithelial lining. The results showed complete radial expansion, little adherence to the tracheal mucosa, and low tissue attachment, as well as high rates of granuloma formation and stent migration. This new model proved to be biocompatible and showed a behavior similar to that of other stents on the market.

Keywords: Prosthesis implantation; Tracheal stenosis; Rabbits; Stents.

Objective: To compare the effects that prone and supine positioning during high-frequency oscillatory ventilation (HFOV) have on oxygenation and lung inflammation, histological injury, and oxidative stress in a rabbit model of acute lung injury (ALI). Methods: Thirty male Norfolk white rabbits were induced to ALI by tracheal saline lavage (30 mL/kg, 38°C). The injury was induced during conventional mechanical ventilation, and ALI was considered confirmed when a PaO2/FiO2 ratio < 100 mmHg was reached. Rabbits were randomly divided into two groups: HFOV in the supine position (SP group, n = 15); and HFOV with prone positioning (PP group, n = 15). For HFOV, the mean airway pressure was initially set at 16 cmH2O. At 30, 60, and 90 min after the start of the HFOV protocol, the mean airway pressure was reduced to 14, 12, and 10 cmH2O, respectively. At 120 min, the animals were returned to or remained in the supine position for an extra 30 min. We evaluated oxygenation indices and histological lung injury scores, as well as TNF-α levels in BAL fluid and lung tissue. Results: After ALI induction, all of the animals showed significant hypoxemia, decreased respiratory system compliance, decreased oxygenation, and increased mean airway pressure in comparison with the baseline values. There were no statistically significant differences between the two groups, at any of the time points evaluated, in terms of the PaO2 or oxygenation index. However, TNF-α levels in BAL fluid were significantly lower in the PP group than in the SP group, as were histological lung injury scores. Conclusions: Prone positioning appears to attenuate inflammatory and histological lung injury during HFOV in rabbits with ALI.

Keywords: Respiration, artificial/adverse effects; Prone position; Lung/physiopathology; Pneumonia; Respiratory distress syndrome, adult; Acute lung injury; Disease models, animal; Rabbits.

Objective: To analyze the treatment strategies that influence the effectiveness of tuberculosis treatment at primary care clinics (PCCs) in Brazil. Methods: This was a descriptive, retrospective epidemiological survey based on the medical records of 588 tuberculosis patients enrolled in the tuberculosis control programs at two PCCs located in the city of Belém, Brazil: Centro de Saúde Escola do Marco (CSEM) and Unidade Básica de Saúde da Pedreira (UBSP). The survey was limited to patients enrolled between January of 2004 and December of 2008. We included only patients between 18 and 59 years of age, and we excluded those who were transferred or were found to have been misdiagnosed. We collected data regarding age, gender, type of treatment (self-administered or supervised), co-infection with HIV, and treatment outcome. The health professionals involved in the tuberculosis control program at the two PCCs were interviewed regarding the strategies used for tuberculosis control and regarding routine clinical care for tuberculosis patients. Results: There were no significant differences between the CSEM and UBSP patients regarding age, gender, or co-infection with HIV. Supervised treatment was used significantly more frequently and the rate of cure was higher at the CSEM than at the UBSP, whereas the rate of treatment noncompliance was higher at the UBSP than at the CSEM. Conclusions: For patients enrolled in tuberculosis control programs at PCCs in Brazil, supervised treatment appears to be an extremely important strategy for reducing the rate of treatment noncompliance.

Keywords: Tuberculosis; Patient dropouts; Patient care planning; Treatment outcome.

Objective: To determine whether COPD patients with diaphragmatic dysfunction present higher risk of mortality than do those without such dysfunction. Methods: We evaluated pulmonary function, diaphragm mobility and quality of life, as well as determining the Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) index, in 42 COPD patients. The patients were allocated to two groups according to the degree to which diaphragm mobility was impaired: low mobility (LM; mobility ≤ 33.99 mm); and high mobility (HM; mobility ≥ 34.00 mm). The BODE index and the quality of life were quantified in both groups. All patients were followed up prospectively for up to 48 months in order to determine the number of deaths resulting from respiratory complications due to COPD. Results: Of the 42 patients evaluated, 20 were allocated to the LM group, and 22 were allocated to the HM group. There were no significant differences between the groups regarding age, lung hyperinflation or quality of life. However, BODE index values were higher in the LM group than in the HM group (p = 0.01). During the 48-month follow-up period, there were four deaths within the population studied, and all of those deaths occurred in the LM group (15.79%; p = 0.02). Conclusions: These findings suggest that COPD patients with diaphragmatic dysfunction, characterized by low diaphragm mobility, have a higher risk of death than do those without such dysfunction.

Keywords: Pulmonary disease, chronic obstructive/mortality; Diaphragm; Exercise tolerance; Quality of life.

Objective: To evaluate the pleurodesis and the lung damage caused by intrapleural silver nitrate or talc in an experimental model in rabbits to consider the use in human beings. Design: 112 rabbits were randomized to receive intrapleural 0.5% silver nitrate or 400 mg/kg talc slurry in 2 ml saline. Eight rabbits in each group were sacrificed 1, 2, 4, 6, 8, 10, or 12 months post injection. The degree of pleurodesis (gross pleural fibrosis and inflammation), lung damage (collapse and edema), and cellular infiltrates were graded on a 0 to 4 scale. Results: The intrapleural injection of silver nitrate produced a better pleurodesis than did the intrapleural injection of talc slurry. The lung damage was moderate 1 month after silver nitrate and greater than after talc. They were similar as from the second month. Conclusions: The better pleurodesis induced by silver nitrate persists for at least one year. The more evident lung damage after silver nitrate was mild with reversible changes which show a clear tendency to normalize with time. For these reasons, the efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.

Keywords: Pleurodesis. Talc. Silver nitrate. Pleural effusion.

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.

Objective: Patients with high cervical spinal cord injury are usually dependent on mechanical ventilation support, which, albeit life saving, is associated with complications and decreased life expectancy because of respiratory infections. Diaphragm pacing stimulation (DPS), sometimes referred to as electric ventilation, induces inhalation by stimulating the inspiratory muscles. Our objective was to highlight the indications for and some aspects of the surgical technique employed in the laparoscopic insertion of the DPS electrodes, as well as to describe five cases of tetraplegic patients submitted to the technique. Methods: Patient selection involved transcutaneous phrenic nerve studies in order to determine whether the phrenic nerves were preserved. The surgical approach was traditional laparoscopy, with four ports. The initial step was electrical mapping in order to locate the "motor points" (the points at which stimulation would cause maximal contraction of the diaphragm). If the diaphragm mapping was successful, four electrodes were implanted into the abdominal surface of the diaphragm, two on each side, to stimulate the branches of the phrenic nerve. Results: Of the five patients, three could breathe using DPS alone for more than 24 h, one could do so for more than 6 h, and one could not do so at all. Conclusions: Although a longer follow-up period is needed in order to reach definitive conclusions, the initial results have been promising. At this writing, most of our patients have been able to remain ventilator-free for long periods of time.

Keywords: Spinal cord injuries; Quadriplegia; Respiration, artificial; Pacemaker, artificial; Diaphragm.

Objective: To test the applicability of a geometric model, adapted to the supine position, for the analysis of respiratory mechanics regarding changes in lateral thoracoabdominal areas in children with asthma. Methods: Nineteen children (mean age, 11.26 ± 1.28 years) performed isovolume maneuvers (IVMs) after maximal inspiration, followed by glottal closure and alternation of airflow between the abdominal and thoracic compartments. The maneuvers were recorded in a digital video camera placed perpendicularly to the movement plane, and the images of interest were selected. The geometric model was traced on each image based on surface landmarks of anatomical references. The traced areas were calculated using a computer program, and the results were converted into metric units (cm2) using a surface landmark of a known area. Relative contributions (RCs) of the subcompartments in relation to their original compartments and to the chest wall (CW) were calculated. Results: The model was based on 55 thoracic IVM images and 55 abdominal IVM images. Areas and subareas were compared between the maneuvers. There were significant differences in all subcompartments (p < 0.001). All of the RCs were significantly different for the CW (p < 0.001) but not for the ratios between the subcompartments and their original compartments. Conclusions: This geometric model, applied in children and adapted to the supine position, was effective in profiling changes in the thoracoabdominal silhouette during the IVMs, and the selected subdivisions were useful for the identification of areas contributing the most and the least to CW composition.

Keywords: Photogrammetry; Respiratory mechanics; Image processing, computer-assisted.

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.

Objective: To study the effects that pneumoperitoneum achieved through carbon dioxide insufflation has on diaphragmatic excursion in pigs. Methods: A total of 14 male Landrace pigs, 30 to 45 days of age and weighing five to seven kilograms each, were used. The sample was randomly and equally divided into two groups: one (n = 7) in which pneumoperitoneum was maintained at 10 mmHg for 60 minutes; and another (n = 7) in which pneumoperitoneum was maintained at 15 mmHg (also for 60 minutes). After anesthetic induction, the animals were intubated. Flow volume was monitored, and the amplitude of diaphragmatic excursion was analyzed using noninvasive ultrasound imaging of the right hemidiaphragm. Results: In both groups, restricted diaphragmatic excursion was observed only during the procedure. There was no statistical difference between the two pressure levels studied. Conclusion: The amplitude of diaphragmatic excursion was restricted during abdominal insufflation, independent of the pressure level (within the 10-15 mmHg range), during the study period.

Keywords: Pneumoperitoneum/chemically induced; Carbon dioxide; Diaphragm; Video-assisted surgery; Swine

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 the diaphragmatic mobility of healthy subjects during incentive spirometry with a volume-oriented device, during incentive spirometry with a flow-oriented device, and during diaphragmatic breathing. To compare men and women in terms of diaphragmatic mobility during these three types of breathing exercises. Methods: We evaluated the pulmonary function and diaphragmatic mobility of 17 adult healthy volunteers (9women and 8 men). Diaphragmatic mobility was measured via ultrasound during diaphragmatic breathing and during the use of the two types of incentive spirometers. Results: Diaphragmatic mobility was significantly greater during the use of the volume-oriented incentive spirometer than during the use of the flow-oriented incentive spirometer (70.16 ± 12.83 mm vs. 63.66 ± 10.82 mm; p = 0.02). Diaphragmatic breathing led to a greater diaphragmatic mobility than did the use of the flow-oriented incentive spirometer (69.62 ± 11.83 mm vs. 63.66 ± 10.82 mm; p = 0.02). During all three types of breathing exercises, the women showed a higher mobility/FVC ratio than did the men. Conclusions: Incentive spirometry with a volume-oriented device and diaphragmatic breathing promoted greater diaphragmatic mobility than did incentive spirometry with a flow-oriented device. Women performed better on the three types of breathing exercises than did men.

Keywords: Diaphragm; Breathing exercises; Respiratory function tests; Ultrasonography; Respiratory muscles.

Objective: The aim of this study was to assess the diaphragm kinetics, respiratory function, and serum dosage of leptin and inflammatory cytokines (IL-6 and TNF-a) in three clinical groups: obese, asthmatic, and healthy. Methods: This is a clinical exploratory study performed on 73 youths (12-24 years of age, 42.5% male) allocated into three groups: obesity (OG, n=33), body mass index (BMIz-score) = +2, asthmatic (AG, n=26) controlled mild asthmatics, classified by GINA, and Healthy Control Group (CG, n=14). The participants were subjected to diaphragmatic ultrasound, spirometry, maximal respiratory pressure, serum leptin levels, and IL-6 and TNF-a whole blood cell culture levels. Results: Diaphragm thickness was higher in OG in comparison to AG and CG (2.0±0.4 vs 1.7±0.5 and 1.6±0.2, both with p<0.05). Maximal voluntary ventilation (MVV) was significantly lower in OG and AG in relation to the CG (82.8±21.4 and 72.5±21.2 vs 102.8±27.3, both with p<0.05). OG has the highest leptin rate among the groups (with the other two groups had p<0.05). All groups had similar TNF-a and IL-6 levels. Conclusion: The muscular hypertrophy found in the diaphragm of the obese individuals can be justified by the increase in respiratory work imposed by the chronic condition of the disease. Such increase in thickness did not occur in controlled mild asthmatics. The IL-6 and TNF-a markers detected no evidence of muscle inflammation, even though leptin was expected to be altered in obese individuals. Both obese and asthmatic patients had lower pulmonary resistance than the healthy ones.

Keywords: Obesity; Asthma; Diaphragm excursion; Diaphragm thickness; Adipokines.

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.