João Salge - Academia.edu (original) (raw)

Papers by João Salge

Research paper thumbnail of 6MWT in Idiopathic Pulmonary Fibrosis (IPF) Patients: Desaturation-Distance Ratio, a New Concept in Evaluating Functional Impairment

B38. CLINICAL ASPECTS OF ILD, 2009

Research paper thumbnail of Tracheal polyp

Jornal brasileiro de pneumologia : publicaça̋o oficial da Sociedade Brasileira de Pneumologia e Tisilogia

Benign tracheal tumors are rare, recurrent papillomatosis being the most common. They often simul... more Benign tracheal tumors are rare, recurrent papillomatosis being the most common. They often simulate obstructive pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, and patients with benign tracheal tumors often undergo long-term treatment for such diseases, without any improvement, Therefore, these tumors should be included in the differential diagnosis in patients presenting tracheobronchial tree obstruction. This report describes the case of a patient with a tracheal polyp. The patient presented symptoms for three years, and the spirometry findings suggested intrathoracic obstruction. The patient presented complete clinical and spirometric recovery after bronchoscopic resection of the tumor.

Research paper thumbnail of Pressure-Volume Curves of Patients with Idiopathic Pulmonary Fibrosis (IPF): Evidence of Small Airway and Alveolar Collapse during Mechanical Ventilation

B38. CLINICAL ASPECTS OF ILD, 2009

Research paper thumbnail of LAM Patients: VEGFD and Lung Functional Impairment

C35. NEW FINDINGS IN LAM, 2009

Research paper thumbnail of The effect of massive weight loss on pulmonary function of morbid obese patients

Respiratory Medicine, 2006

Study objectives: To test if morbid obesity causes pulmonary function changes and if massive weig... more Study objectives: To test if morbid obesity causes pulmonary function changes and if massive weight loss have effect on pulmonary function (especially in subjects with BMIX60 kg/m 2 ). Participants: Thirty-nine morbid obese subjects before and after massive weight loss. Measurements and results: Patients had baseline BMIX40 kg/m 2 , pulmonary function test (PFT) before and after surgery for gastric volume reduction and massive weight loss, and presented no complaints unrelated to obesity. Based on initial BMI, the patients were dividied in groups A (BMI 40-59.9 kg/m 2 ) and B (BMIX60 kg/m 2 ). Initially, group A (n ¼ 28) had normal PFT, however group B (n ¼ 11) presented FVC and FEV 1 measurements in the lowest limit of normality (with normal FEV 1 /FVC), significantly different from group A. After massive weight loss, the group B compared to A had a significant improvement in FVC (23.7% vs. 9.7%, P ¼ 0:012) and FEV 1 (25.6% vs. 9.1%, P ¼ 0:006); thus the initial difference in FVC and FEV 1 between groups no longer existed after weight loss. Conclusions: These results point out that the severe morbid obesity (BMIX60 kg/m 2 ) may lead to pulmonary function impairment and presents more prominent pulmonary function gain after massive weight reduction. The possible clinical implications of these results are that PFT abnormalities in subjects with BMIo60 kg/ m 2 should probably be interpreted as consequence of intrinsic respiratory disease and that severe morbid obese patients may be encouraged to lose weight to improve their pulmonary function, especially those with concomitant pulmonary disorders.

Research paper thumbnail of *

Jornal Brasileiro de Pneumologia, 2014

Objective: Respiratory complications are the main causes of morbidity and mortality in patients w... more Objective: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. Methods: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. Results: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. Conclusions: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.

Research paper thumbnail of Burnt sugarcane harvesting: Particulate matter exposure and the effects on lung function, oxidative stress, and urinary 1-hydroxypyrene

Science of The Total Environment, 2012

► This study assesses PM 2.5 exposure and its metabolic and respiratory impacts. ► PM 2.5 increas... more ► This study assesses PM 2.5 exposure and its metabolic and respiratory impacts. ► PM 2.5 increased in sugarcane fields and in the town during the harvesting period. ► Both studied groups exhibited elevated oxidative stress markers during the harvest. ► The lung function of both studied groups was reduced during the harvest. ► There is a need to discuss the process of non-mechanised burnt sugarcane harvesting. a b s t r a c t Non-mechanised sugarcane harvesting preceded by burning exposes workers and the people of neighbouring towns to high concentrations of pollutants. This study was aimed to evaluate the respiratory symptoms, lung function and oxidative stress markers in sugarcane workers and the residents of Mendonça, an agricultural town in Brazil, during the non-harvesting and harvesting periods and to assess the population and individual exposures to fine particulate matter (PM 2.5 ). Sugarcane workers and healthy volunteers were evaluated with two respiratory symptom questionnaires, spirometry, urinary 1-hydroxypyrene levels, and the measurement of antioxidant enzymes and plasma malonaldehyde during the non-harvesting and harvesting periods. The environmental assessment was determined from PM 2.5 concentration. PM 2.5 level increased from 8 μg/m³ during the non-harvesting period to 23.5 μg/m³ in the town and 61 μg/m³ on the plantations during the harvesting period. Wheezing, coughing, sneezing, and breathlessness increased significantly in both groups during the harvesting period, but more markedly in workers. A decrease in lung function and antioxidant enzyme activity was observed in both populations during harvesting; this decrease was greater among the sugarcane workers. The urinary 1-hydroxypyrene levels only increased in the sugarcane workers during the harvesting period. The malonaldehyde levels were elevated in both groups, with a higher increase observed in the workers. This research demonstrates the exposure of sugarcane workers and the inhabitants of a neighbouring town to high PM 2.5 concentrations during the sugarcane harvest period. This exposure was higher among the sugarcane workers, as illustrated by both higher PM 2.5 concentrations in the sugarcane fields and higher urinary 1-hydroxypyrene levels in the volunteers in this group. The higher incidence of respiratory symptoms, j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / s c i t o t e n v greater decrease in lung function and more marked elevation of oxidative stress markers among the sugarcane workers during the harvest confirms the greater effect magnitude in this population and a dose-dependent relationship between pollution and the observed effects.

Research paper thumbnail of Pólipo traqueal

Jornal Brasileiro de Pneumologia, 2007

Tumores benignos primários da traquéia são raros, sendo o mais freqüente a papilomatose benigna r... more Tumores benignos primários da traquéia são raros, sendo o mais freqüente a papilomatose benigna recorrente. Muitas vezes simulam doenças pulmonares obstrutivas, como asma e doença pulmonar obstrutiva crônica, sendo os pacientes tratados como portadores de tais doenças por longo período sem apresentar melhora. Deve-se, portanto, incluí-los no diagnóstico diferencial dos quadros de obstrução da árvore traqueobrônquica. Relata-se um caso de paciente com pólipo traqueal com evolução de três anos e espirometria evidenciando padrão de obstrução intratorácica variável, que evoluiu com melhora clínica e funcional completa após ressecção por via broncoscópica.

Research paper thumbnail of A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis patients on mechanical ventilation: clinical implications

Clinics (São Paulo, Brazil), 2011

Respiratory pressure-volume curves fitted to exponential equations have been used to assess disea... more Respiratory pressure-volume curves fitted to exponential equations have been used to assess disease severity and prognosis in spontaneously breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have been used to fit pressure-volume curves for mechanically ventilated patients but not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and an exponential model to fit pressure-volume curves from mechanically ventilated patients with idiopathic pulmonary fibrosis. Six idiopathic pulmonary fibrosis patients and five controls underwent inflation pressure-volume curves using the constant-flow technique during general anesthesia prior to open lung biopsy or thymectomy. We identified the lower and upper inflection points and fit the curves with an exponential equation, V = A-B.e-k.P, and a sigmoid equation, V = a+b/(1+e-(P-c)/d). The mean lower inflection point for idiopathic pulmonary fibrosis patients was significantly higher (10.5 ± 5.7 cm H2O) t...

Research paper thumbnail of The lung in paracoccidioidomycosis: new insights into old problems

Clinics (São Paulo, Brazil), 2013

Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, pat... more Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related ...

Research paper thumbnail of Infection as an independent risk factor for mortality in the surgical intensive care unit

Clinics (São Paulo, Brazil), 2013

Medical and surgical intensive care unit patients represent two different populations and require... more Medical and surgical intensive care unit patients represent two different populations and require different treatment approaches. The aim of this study was to investigate the parameters associated with mortality in medical and surgical intensive care units. This was a prospective cohort study of adult patients admitted to a medical and surgical intensive care unit teaching hospital over an 11-month period. Factors associated with mortality were explored using logistic regression analysis. In total, 827 admissions were observed, and 525 patients >18 years old and with a length of stay >24 h were analyzed. Of these patients, 227 were in the medical and 298 were in the surgical intensive care unit. The surgical patients were older (p<0.01) and had shorter lengths of stay (p<0.01). The mortality in the intensive care unit (35.1 vs. 26.2, p = 0.02) and hospital (48.8 vs. 35.5, p<0.01) was higher for medical patients. For patients in the surgical intensive care unit, death ...

Research paper thumbnail of Disfunção diafragmática e mortalidade em pacientes portadores de DPOC

Jornal Brasileiro de Pneumologia, 2009

Resumo Objetivo: Verificar se indivíduos portadores de DPOC com disfunção diafragmática apresenta... more Resumo Objetivo: Verificar se indivíduos portadores de DPOC com disfunção diafragmática apresentam maior risco de mortalidade quando comparados àqueles sem disfunção diafragmática. Métodos: Foi avaliada a função pulmonar, a mobilidade diafragmática, a qualidade de vida e o índice conhecido como Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) em 42 pacientes portadores de DPOC. Os pacientes foram alocados em dois grupos de acordo com a gravidade do acometimento da mobilidade do diafragma: grupo de baixa mobilidade (BM; mobilidade ≤ 33,99 mm) e grupo de alta mobilidade (AM; mobilidade ≥ 34,00 mm). O índice BODE e a qualidade de vida foram quantificados nos dois grupos. Todos os pacientes foram acompanhados prospectivamente por um período de até 48 meses a fim de identificarmos o número de óbitos decorrentes de complicações respiratórias devido a DPOC. Resultados: Dos 42 pacientes avaliados, 20 foram classificados no grupo BM, e 22 foram alocados no grupo AM. Não houve diferenças significativas quanto à faixa etária, hiperinsuflação pulmonar e fatores relacionados à qualidade de vida entre os grupos. Entretanto, o grupo BM apresentou maior pontuação no índice BODE em relação ao grupo AM (p = 0,01). O acompanhamento dos pacientes ao longo de 48 meses permitiu identificar quatro óbitos na população estudada, sendo todos os casos no grupo BM (15,79%; p = 0,02). Conclusões: Esses resultados sugerem que pacientes portadores de DPOC com disfunção diafragmática, caracterizada por uma baixa mobilidade do diafragma, apresentam maior risco de mortalidade quando comparados àqueles sem disfunção diafragmática. Descritores: Doença pulmonar obstrutiva crônica/mortalidade; Diafragma; Tolerância ao exercício; Qualidade de vida.

Research paper thumbnail of Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension

PLoS ONE, 2014

Background: Pulmonary arterial hypertension is a progressive disease that is characterized by dys... more Background: Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH. Methods: The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls. Results: PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO 2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output. Conclusion: Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH. OPEN ACCESS Citation: Breda AP, Pereira de Albuquerque AL, Jardim C, Morinaga LK, Suesada MM, et al. (2014) Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension. PLoS ONE 9(12): e114101.

Research paper thumbnail of Lung Resection Improves the Quality of Life of Patients With Symptomatic Bronchiectasis

The Annals of Thoracic Surgery, 2014

Background. Bronchiectasis is a significant cause of morbidity. Surgical resection is a treatment... more Background. Bronchiectasis is a significant cause of morbidity. Surgical resection is a treatment option, but its main outcomes regarding quality of life (QOL) and physiologic consequences have not been addressed previously, to our knowledge. We aimed to evaluate the effect of surgical procedures on QOL, exercise capacity, and lung function in patients with bronchiectasis in whom medical treatment was unsuccessful.

Research paper thumbnail of Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Respirology, 2008

Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility ... more Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. COPD patients with pulmonary hyperinflation (n = 54) and healthy subjects (n = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. COPD patients had less diaphragm mobility than did healthy individuals (36.5 +/- 10.9 mm vs 46.3 +/- 9.5 mm, P = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; RV/TLC: r = -0.76, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), moderately with airway obstruction (FEV(1): r = 0.55, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; airway resistance: r = -0.32, P = 0.02) and weakly with pulmonary hyperinflation (TLC: r = -0.28, P = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11, P = 0.43; maximal expiratory pressure: r = 0.03, P = 0.80). The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.

Research paper thumbnail of A pilot study assessing the effect of bronchodilator on dynamic hyperinflation in LAM

Respiratory Medicine, 2013

Introduction: Positive responses to bronchodilators (BDs) on spirometry can be found in up to 30%... more Introduction: Positive responses to bronchodilators (BDs) on spirometry can be found in up to 30% of patients with lymphangioleiomyomatosis (LAM). However, no previous studies have investigated the impact of BDs on exercise outcomes, including dynamic hyperinflation (DH). Methods: A randomised, double-blind, placebo-controlled, crossover trial was conducted on 38 patients with LAM, comparing inhaled placebo versus salbutamol. Pulmonary function tests and a cycle endurance test at 75% of the maximal work capacity, with evaluation of DH by serial measurement of inspiratory capacity (IC), which was the primary endpoint, were performed after each intervention. Results: Although salbutamol produced a slight improvement in airway obstruction, compared with placebo, there was no significant variation in resting IC or air trapping. A total of 18% of the patients met the criteria for a positive response to BD. During submaximal exercise, BD did not reduce DH or dyspnoea nor did it improve exercise tolerance in the entire population. In addition, BD produced only slight improvement in FEV 1 and air trapping in patients who had DH during incremental cardiopulmonary exercise testing, without the beneficial effects on exercise outcomes. Conclusions: Although salbutamol produced a slight improvement in airway obstruction, it did not lead to a reduction in DH or increase in exercise tolerance in patients with LAM. Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC); www.ensaiosclinicos. gov.br; registration number: RBR-49sk2j. ª

Research paper thumbnail of Functional implications of BAL in the presence of restrictive or obstructive lung disease

Respiratory Medicine, 2007

We conclude that standardized BAL, like the one used in our study, does not result in an increase... more We conclude that standardized BAL, like the one used in our study, does not result in an increased risk for ventilatory impairment compared to bronchoscopy itself, independently of the presence of previous respiratory disease.

Research paper thumbnail of Esophageal involvement and interstitial lung disease in mixed connective tissue disease

Respiratory Medicine, 2009

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonar... more Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa&#39;s classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p&lt;0.01) and among patients with severe motor dysfunction (90% vs. 35%; p&lt;0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Research paper thumbnail of P4.57 Effects of air stacking on peak cough flows and forced vital capacity in patients with muscular dystrophy and spinal muscular atrophy

Neuromuscular Disorders, 2011

myopathy called relatively relaxed or ryr. Among other hits, we found upregulation of several gen... more myopathy called relatively relaxed or ryr. Among other hits, we found upregulation of several genes associated with oxidative stress. We thus hypothesized that abnormalities in oxidative stress may be a key aspect of this disease. We then tested our hypothesis using several measures of oxidative stress in ryr, and found significant increases in all of them. Based on these data, we next studied the effect of antioxidant therapy on the ryr motor phenotype. We determined that N-acetylcysteine reduced oxidative stress, improved endurance, and ameliorated certain pathologic changes in the fish. Finally, we related these findings back to patients with RYR1 mutations. Using myocytes derived from patient biopsies from a range of RYR1 myopathies, we detected significantly increased levels of basal oxidative stress and increased sensitivity to oxidant exposure. Both abnormalities were reversed with N-acetylcysteine exposure. In all, we demonstrated that increased oxidative stress is an important aspect of the pathogenesis of RYR1-related myopathies, and showed that antioxidant treatment is a viable potential treatment strategy for patients affected with these conditions. Developing aptamer drugs for a new therapy for amyotrophic lateral sclerosis (ALS) is our ultimate goal. The aptamers are nanomolar affinity, water-soluble RNA inhibitors of the alpha-amino-3-hydroxy-5-methyl-4isoxazole propionate (AMPA) receptors, a subtype of glutamate ion channel receptors. Excessive activation of AMPA receptors induces calcium-mediated excitotoxicity, one of the leading causes underlying the selective death of motor neurons in ALS. To date, we have successfully identified aptamers that inhibit every AMPA receptor subunit -these are competitive and noncompetitive type. We have also identified a noncompetitive aptamer that exclusively inhibits GluR2, a key AMPA receptor subunit that mediates excitotoxicity. Because these aptamers possess unparalleled properties, i.e. nanomolar potency, subunit or subtype selectivity and water solubility, as compared to all other existing AMPA receptor inhibitors, they are promising drug candidates for a new and potentially more effective ALS therapy. To turn these aptamers into potentially useful drugs, we have also successfully generated a class of chemically modified aptamers resistant to ribonucleases so that these aptamers can be tested in vivo. This is because, unmodified, RNA aptamers have limited stability in vivo due to their inherent sensitivity to ribonucleases, the enzymes that catalyze their degradation. Therefore, the aptamers we discovered represent water-soluble, highly potent and selective templates for design of better inhibitors as drug candidates for a potential new ALS therapy.

Research paper thumbnail of Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions

CHEST Journal, 2011

Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of f... more Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), whereas dyspnea decreased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Statistical correlations (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.

Research paper thumbnail of 6MWT in Idiopathic Pulmonary Fibrosis (IPF) Patients: Desaturation-Distance Ratio, a New Concept in Evaluating Functional Impairment

B38. CLINICAL ASPECTS OF ILD, 2009

Research paper thumbnail of Tracheal polyp

Jornal brasileiro de pneumologia : publicaça̋o oficial da Sociedade Brasileira de Pneumologia e Tisilogia

Benign tracheal tumors are rare, recurrent papillomatosis being the most common. They often simul... more Benign tracheal tumors are rare, recurrent papillomatosis being the most common. They often simulate obstructive pulmonary diseases, such as asthma and chronic obstructive pulmonary disease, and patients with benign tracheal tumors often undergo long-term treatment for such diseases, without any improvement, Therefore, these tumors should be included in the differential diagnosis in patients presenting tracheobronchial tree obstruction. This report describes the case of a patient with a tracheal polyp. The patient presented symptoms for three years, and the spirometry findings suggested intrathoracic obstruction. The patient presented complete clinical and spirometric recovery after bronchoscopic resection of the tumor.

Research paper thumbnail of Pressure-Volume Curves of Patients with Idiopathic Pulmonary Fibrosis (IPF): Evidence of Small Airway and Alveolar Collapse during Mechanical Ventilation

B38. CLINICAL ASPECTS OF ILD, 2009

Research paper thumbnail of LAM Patients: VEGFD and Lung Functional Impairment

C35. NEW FINDINGS IN LAM, 2009

Research paper thumbnail of The effect of massive weight loss on pulmonary function of morbid obese patients

Respiratory Medicine, 2006

Study objectives: To test if morbid obesity causes pulmonary function changes and if massive weig... more Study objectives: To test if morbid obesity causes pulmonary function changes and if massive weight loss have effect on pulmonary function (especially in subjects with BMIX60 kg/m 2 ). Participants: Thirty-nine morbid obese subjects before and after massive weight loss. Measurements and results: Patients had baseline BMIX40 kg/m 2 , pulmonary function test (PFT) before and after surgery for gastric volume reduction and massive weight loss, and presented no complaints unrelated to obesity. Based on initial BMI, the patients were dividied in groups A (BMI 40-59.9 kg/m 2 ) and B (BMIX60 kg/m 2 ). Initially, group A (n ¼ 28) had normal PFT, however group B (n ¼ 11) presented FVC and FEV 1 measurements in the lowest limit of normality (with normal FEV 1 /FVC), significantly different from group A. After massive weight loss, the group B compared to A had a significant improvement in FVC (23.7% vs. 9.7%, P ¼ 0:012) and FEV 1 (25.6% vs. 9.1%, P ¼ 0:006); thus the initial difference in FVC and FEV 1 between groups no longer existed after weight loss. Conclusions: These results point out that the severe morbid obesity (BMIX60 kg/m 2 ) may lead to pulmonary function impairment and presents more prominent pulmonary function gain after massive weight reduction. The possible clinical implications of these results are that PFT abnormalities in subjects with BMIo60 kg/ m 2 should probably be interpreted as consequence of intrinsic respiratory disease and that severe morbid obese patients may be encouraged to lose weight to improve their pulmonary function, especially those with concomitant pulmonary disorders.

Research paper thumbnail of *

Jornal Brasileiro de Pneumologia, 2014

Objective: Respiratory complications are the main causes of morbidity and mortality in patients w... more Objective: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. Methods: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. Results: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. Conclusions: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.

Research paper thumbnail of Burnt sugarcane harvesting: Particulate matter exposure and the effects on lung function, oxidative stress, and urinary 1-hydroxypyrene

Science of The Total Environment, 2012

► This study assesses PM 2.5 exposure and its metabolic and respiratory impacts. ► PM 2.5 increas... more ► This study assesses PM 2.5 exposure and its metabolic and respiratory impacts. ► PM 2.5 increased in sugarcane fields and in the town during the harvesting period. ► Both studied groups exhibited elevated oxidative stress markers during the harvest. ► The lung function of both studied groups was reduced during the harvest. ► There is a need to discuss the process of non-mechanised burnt sugarcane harvesting. a b s t r a c t Non-mechanised sugarcane harvesting preceded by burning exposes workers and the people of neighbouring towns to high concentrations of pollutants. This study was aimed to evaluate the respiratory symptoms, lung function and oxidative stress markers in sugarcane workers and the residents of Mendonça, an agricultural town in Brazil, during the non-harvesting and harvesting periods and to assess the population and individual exposures to fine particulate matter (PM 2.5 ). Sugarcane workers and healthy volunteers were evaluated with two respiratory symptom questionnaires, spirometry, urinary 1-hydroxypyrene levels, and the measurement of antioxidant enzymes and plasma malonaldehyde during the non-harvesting and harvesting periods. The environmental assessment was determined from PM 2.5 concentration. PM 2.5 level increased from 8 μg/m³ during the non-harvesting period to 23.5 μg/m³ in the town and 61 μg/m³ on the plantations during the harvesting period. Wheezing, coughing, sneezing, and breathlessness increased significantly in both groups during the harvesting period, but more markedly in workers. A decrease in lung function and antioxidant enzyme activity was observed in both populations during harvesting; this decrease was greater among the sugarcane workers. The urinary 1-hydroxypyrene levels only increased in the sugarcane workers during the harvesting period. The malonaldehyde levels were elevated in both groups, with a higher increase observed in the workers. This research demonstrates the exposure of sugarcane workers and the inhabitants of a neighbouring town to high PM 2.5 concentrations during the sugarcane harvest period. This exposure was higher among the sugarcane workers, as illustrated by both higher PM 2.5 concentrations in the sugarcane fields and higher urinary 1-hydroxypyrene levels in the volunteers in this group. The higher incidence of respiratory symptoms, j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / s c i t o t e n v greater decrease in lung function and more marked elevation of oxidative stress markers among the sugarcane workers during the harvest confirms the greater effect magnitude in this population and a dose-dependent relationship between pollution and the observed effects.

Research paper thumbnail of Pólipo traqueal

Jornal Brasileiro de Pneumologia, 2007

Tumores benignos primários da traquéia são raros, sendo o mais freqüente a papilomatose benigna r... more Tumores benignos primários da traquéia são raros, sendo o mais freqüente a papilomatose benigna recorrente. Muitas vezes simulam doenças pulmonares obstrutivas, como asma e doença pulmonar obstrutiva crônica, sendo os pacientes tratados como portadores de tais doenças por longo período sem apresentar melhora. Deve-se, portanto, incluí-los no diagnóstico diferencial dos quadros de obstrução da árvore traqueobrônquica. Relata-se um caso de paciente com pólipo traqueal com evolução de três anos e espirometria evidenciando padrão de obstrução intratorácica variável, que evoluiu com melhora clínica e funcional completa após ressecção por via broncoscópica.

Research paper thumbnail of A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis patients on mechanical ventilation: clinical implications

Clinics (São Paulo, Brazil), 2011

Respiratory pressure-volume curves fitted to exponential equations have been used to assess disea... more Respiratory pressure-volume curves fitted to exponential equations have been used to assess disease severity and prognosis in spontaneously breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have been used to fit pressure-volume curves for mechanically ventilated patients but not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and an exponential model to fit pressure-volume curves from mechanically ventilated patients with idiopathic pulmonary fibrosis. Six idiopathic pulmonary fibrosis patients and five controls underwent inflation pressure-volume curves using the constant-flow technique during general anesthesia prior to open lung biopsy or thymectomy. We identified the lower and upper inflection points and fit the curves with an exponential equation, V = A-B.e-k.P, and a sigmoid equation, V = a+b/(1+e-(P-c)/d). The mean lower inflection point for idiopathic pulmonary fibrosis patients was significantly higher (10.5 ± 5.7 cm H2O) t...

Research paper thumbnail of The lung in paracoccidioidomycosis: new insights into old problems

Clinics (São Paulo, Brazil), 2013

Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, pat... more Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related ...

Research paper thumbnail of Infection as an independent risk factor for mortality in the surgical intensive care unit

Clinics (São Paulo, Brazil), 2013

Medical and surgical intensive care unit patients represent two different populations and require... more Medical and surgical intensive care unit patients represent two different populations and require different treatment approaches. The aim of this study was to investigate the parameters associated with mortality in medical and surgical intensive care units. This was a prospective cohort study of adult patients admitted to a medical and surgical intensive care unit teaching hospital over an 11-month period. Factors associated with mortality were explored using logistic regression analysis. In total, 827 admissions were observed, and 525 patients >18 years old and with a length of stay >24 h were analyzed. Of these patients, 227 were in the medical and 298 were in the surgical intensive care unit. The surgical patients were older (p<0.01) and had shorter lengths of stay (p<0.01). The mortality in the intensive care unit (35.1 vs. 26.2, p = 0.02) and hospital (48.8 vs. 35.5, p<0.01) was higher for medical patients. For patients in the surgical intensive care unit, death ...

Research paper thumbnail of Disfunção diafragmática e mortalidade em pacientes portadores de DPOC

Jornal Brasileiro de Pneumologia, 2009

Resumo Objetivo: Verificar se indivíduos portadores de DPOC com disfunção diafragmática apresenta... more Resumo Objetivo: Verificar se indivíduos portadores de DPOC com disfunção diafragmática apresentam maior risco de mortalidade quando comparados àqueles sem disfunção diafragmática. Métodos: Foi avaliada a função pulmonar, a mobilidade diafragmática, a qualidade de vida e o índice conhecido como Body mass index, airway Obstruction, Dyspnea, and Exercise capacity (BODE) em 42 pacientes portadores de DPOC. Os pacientes foram alocados em dois grupos de acordo com a gravidade do acometimento da mobilidade do diafragma: grupo de baixa mobilidade (BM; mobilidade ≤ 33,99 mm) e grupo de alta mobilidade (AM; mobilidade ≥ 34,00 mm). O índice BODE e a qualidade de vida foram quantificados nos dois grupos. Todos os pacientes foram acompanhados prospectivamente por um período de até 48 meses a fim de identificarmos o número de óbitos decorrentes de complicações respiratórias devido a DPOC. Resultados: Dos 42 pacientes avaliados, 20 foram classificados no grupo BM, e 22 foram alocados no grupo AM. Não houve diferenças significativas quanto à faixa etária, hiperinsuflação pulmonar e fatores relacionados à qualidade de vida entre os grupos. Entretanto, o grupo BM apresentou maior pontuação no índice BODE em relação ao grupo AM (p = 0,01). O acompanhamento dos pacientes ao longo de 48 meses permitiu identificar quatro óbitos na população estudada, sendo todos os casos no grupo BM (15,79%; p = 0,02). Conclusões: Esses resultados sugerem que pacientes portadores de DPOC com disfunção diafragmática, caracterizada por uma baixa mobilidade do diafragma, apresentam maior risco de mortalidade quando comparados àqueles sem disfunção diafragmática. Descritores: Doença pulmonar obstrutiva crônica/mortalidade; Diafragma; Tolerância ao exercício; Qualidade de vida.

Research paper thumbnail of Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension

PLoS ONE, 2014

Background: Pulmonary arterial hypertension is a progressive disease that is characterized by dys... more Background: Pulmonary arterial hypertension is a progressive disease that is characterized by dyspnea and exercise intolerance. Impairment in skeletal muscle has recently been described in PAH, although the degree to which this impairment is solely determined by the hemodynamic profile remains uncertain. The aim of this study was to verify the association of structural and functional skeletal muscle characteristics with maximum exercise in PAH. Methods: The exercise capacity, body composition, CT area of limb muscle, quality of life, quadriceps biopsy and hemodynamics of 16 PAH patients were compared with those of 10 controls. Results: PAH patients had a significantly poorer quality of life, reduced percentage of lean body mass, reduced respiratory muscle strength, reduced resistance and strength of quadriceps and increased functional limitation at 6MWT and CPET. VO 2 max was correlated with muscular variables and cardiac output. Bivariate linear regression models showed that the association between muscular structural and functional variables remained significant even after correcting for cardiac output. Conclusion: Our study showed the coexistence of ventilatory and quadriceps weakness in face of exercise intolerance in the same group of PAH patients. More interestingly, it is the first time that the independent association between muscular pattern and maximum exercise capacity is evidenced in PAH, independently of cardiac index highlighting the importance of considering rehabilitation in the treatment strategy for PAH. OPEN ACCESS Citation: Breda AP, Pereira de Albuquerque AL, Jardim C, Morinaga LK, Suesada MM, et al. (2014) Skeletal Muscle Abnormalities in Pulmonary Arterial Hypertension. PLoS ONE 9(12): e114101.

Research paper thumbnail of Lung Resection Improves the Quality of Life of Patients With Symptomatic Bronchiectasis

The Annals of Thoracic Surgery, 2014

Background. Bronchiectasis is a significant cause of morbidity. Surgical resection is a treatment... more Background. Bronchiectasis is a significant cause of morbidity. Surgical resection is a treatment option, but its main outcomes regarding quality of life (QOL) and physiologic consequences have not been addressed previously, to our knowledge. We aimed to evaluate the effect of surgical procedures on QOL, exercise capacity, and lung function in patients with bronchiectasis in whom medical treatment was unsuccessful.

Research paper thumbnail of Air trapping: The major factor limiting diaphragm mobility in chronic obstructive pulmonary disease patients

Respirology, 2008

Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility ... more Patients with COPD can have impaired diaphragm mechanics. A new method of assessing the mobility of the diaphragm, using ultrasound, has recently been validated. This study evaluated the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. COPD patients with pulmonary hyperinflation (n = 54) and healthy subjects (n = 20) were studied. Patients were tested for pulmonary function, maximal respiratory pressures and diaphragm mobility using ultrasound to measure the craniocaudal displacement of the left branch of the portal vein. COPD patients had less diaphragm mobility than did healthy individuals (36.5 +/- 10.9 mm vs 46.3 +/- 9.5 mm, P = 0.001). In COPD patients, diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; RV/TLC: r = -0.76, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), moderately with airway obstruction (FEV(1): r = 0.55, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; airway resistance: r = -0.32, P = 0.02) and weakly with pulmonary hyperinflation (TLC: r = -0.28, P = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11, P = 0.43; maximal expiratory pressure: r = 0.03, P = 0.80). The results of this study suggest that the reduction in diaphragm mobility in COPD patients is mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.

Research paper thumbnail of A pilot study assessing the effect of bronchodilator on dynamic hyperinflation in LAM

Respiratory Medicine, 2013

Introduction: Positive responses to bronchodilators (BDs) on spirometry can be found in up to 30%... more Introduction: Positive responses to bronchodilators (BDs) on spirometry can be found in up to 30% of patients with lymphangioleiomyomatosis (LAM). However, no previous studies have investigated the impact of BDs on exercise outcomes, including dynamic hyperinflation (DH). Methods: A randomised, double-blind, placebo-controlled, crossover trial was conducted on 38 patients with LAM, comparing inhaled placebo versus salbutamol. Pulmonary function tests and a cycle endurance test at 75% of the maximal work capacity, with evaluation of DH by serial measurement of inspiratory capacity (IC), which was the primary endpoint, were performed after each intervention. Results: Although salbutamol produced a slight improvement in airway obstruction, compared with placebo, there was no significant variation in resting IC or air trapping. A total of 18% of the patients met the criteria for a positive response to BD. During submaximal exercise, BD did not reduce DH or dyspnoea nor did it improve exercise tolerance in the entire population. In addition, BD produced only slight improvement in FEV 1 and air trapping in patients who had DH during incremental cardiopulmonary exercise testing, without the beneficial effects on exercise outcomes. Conclusions: Although salbutamol produced a slight improvement in airway obstruction, it did not lead to a reduction in DH or increase in exercise tolerance in patients with LAM. Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC); www.ensaiosclinicos. gov.br; registration number: RBR-49sk2j. ª

Research paper thumbnail of Functional implications of BAL in the presence of restrictive or obstructive lung disease

Respiratory Medicine, 2007

We conclude that standardized BAL, like the one used in our study, does not result in an increase... more We conclude that standardized BAL, like the one used in our study, does not result in an increased risk for ventilatory impairment compared to bronchoscopy itself, independently of the presence of previous respiratory disease.

Research paper thumbnail of Esophageal involvement and interstitial lung disease in mixed connective tissue disease

Respiratory Medicine, 2009

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonar... more Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa&#39;s classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p&lt;0.01) and among patients with severe motor dysfunction (90% vs. 35%; p&lt;0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Research paper thumbnail of P4.57 Effects of air stacking on peak cough flows and forced vital capacity in patients with muscular dystrophy and spinal muscular atrophy

Neuromuscular Disorders, 2011

myopathy called relatively relaxed or ryr. Among other hits, we found upregulation of several gen... more myopathy called relatively relaxed or ryr. Among other hits, we found upregulation of several genes associated with oxidative stress. We thus hypothesized that abnormalities in oxidative stress may be a key aspect of this disease. We then tested our hypothesis using several measures of oxidative stress in ryr, and found significant increases in all of them. Based on these data, we next studied the effect of antioxidant therapy on the ryr motor phenotype. We determined that N-acetylcysteine reduced oxidative stress, improved endurance, and ameliorated certain pathologic changes in the fish. Finally, we related these findings back to patients with RYR1 mutations. Using myocytes derived from patient biopsies from a range of RYR1 myopathies, we detected significantly increased levels of basal oxidative stress and increased sensitivity to oxidant exposure. Both abnormalities were reversed with N-acetylcysteine exposure. In all, we demonstrated that increased oxidative stress is an important aspect of the pathogenesis of RYR1-related myopathies, and showed that antioxidant treatment is a viable potential treatment strategy for patients affected with these conditions. Developing aptamer drugs for a new therapy for amyotrophic lateral sclerosis (ALS) is our ultimate goal. The aptamers are nanomolar affinity, water-soluble RNA inhibitors of the alpha-amino-3-hydroxy-5-methyl-4isoxazole propionate (AMPA) receptors, a subtype of glutamate ion channel receptors. Excessive activation of AMPA receptors induces calcium-mediated excitotoxicity, one of the leading causes underlying the selective death of motor neurons in ALS. To date, we have successfully identified aptamers that inhibit every AMPA receptor subunit -these are competitive and noncompetitive type. We have also identified a noncompetitive aptamer that exclusively inhibits GluR2, a key AMPA receptor subunit that mediates excitotoxicity. Because these aptamers possess unparalleled properties, i.e. nanomolar potency, subunit or subtype selectivity and water solubility, as compared to all other existing AMPA receptor inhibitors, they are promising drug candidates for a new and potentially more effective ALS therapy. To turn these aptamers into potentially useful drugs, we have also successfully generated a class of chemically modified aptamers resistant to ribonucleases so that these aptamers can be tested in vivo. This is because, unmodified, RNA aptamers have limited stability in vivo due to their inherent sensitivity to ribonucleases, the enzymes that catalyze their degradation. Therefore, the aptamers we discovered represent water-soluble, highly potent and selective templates for design of better inhibitors as drug candidates for a potential new ALS therapy.

Research paper thumbnail of Improvements in the 6-Min Walk Test and Spirometry Following Thoracentesis for Symptomatic Pleural Effusions

CHEST Journal, 2011

Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of f... more Impairment in pulmonary capacity due to pleural effusion compromises daily activity. Removal of fluid improves symptoms, but the impact, especially on exercise capacity, has not been determined. Twenty-five patients with unilateral pleural effusion documented by chest radiograph were included. The 6-min walk test, Borg modified dyspnea score, FVC, and FEV(1) were analyzed before and 48 h after the removal of large pleural effusions. The mean fluid removed was 1,564 ± 695 mL. After the procedure, values of FVC, FEV(1), and 6-min walk distance increased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), whereas dyspnea decreased (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). Statistical correlations (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001) between 6-min walk distance and FVC (r = 0.725) and between 6-min walk distance and FEV(1) (r = 0.661) were observed. Correlations also were observed between the deltas (prethoracentesis × postthoracentesis) of the 6-min walk test and the percentage of FVC (r = 0.450) and of FEV(1) (r = 0.472) divided by the volume of fluid removed (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). In addition to the improvement in lung function after thoracentesis, the benefits of fluid removal are more evident in situations of exertion, allowing better readaptation of patients to routine activities.