Obese obstructive sleep apnea patients with tonsil hypertrophy submitted to tonsillectomy

The physiopathology of obstructive sleep apnea-hypopnea syndrome (OSAHS) is multifactorial and obesity has been shown to be one of the main factors correlated with its occurrence. In obese patients with anatomical alterations of the upper airways it is often difficult to predict success for surgical correction since obesity is a limiting factor. Therefore, the aim of the present study was to evaluate the results of tonsillectomy in a specific group of patients, i.e., obese OSAHS patients with tonsil hypertrophy. Seven OSAHS patients with moderate obesity with obstructive palatine tonsil hypertrophy were submitted to tonsillectomy. All patients were submitted to pre- and postoperative appraisal of body mass index, otorhinolaryngology examination and polysomnography. Patients' average age was 36.4 ± 10.3 years and average preoperative body mass index was 36.6 ± 6.3 kg/m². Postoperative weight did not differ significantly from preoperative weight (P = 0.27). Average preoperative apnea and hypopnea index (AHI) was 81 ± 26/h and postoperative AHI was 23 ± 18/h (P = 0.0005). Average preoperative minimum oxyhemoglobin saturation (SaO2 min) was 69 ± 14% and the postoperative value was 83 ± 3% (P = 0.038). In relation to AHI, 6 (86%) of the 7 patients studied showed a reduction of 50% in relation to preoperative level and of these, 4 (57%) presented AHI of less than 20%. Only one patient presented a reduction of less than 50% in AHI, but even so showed improved SaO2 min. Tonsillectomy treatment for OSAHS in obese patients with obstructive palatine tonsil hypertrophy caused a significant reduction in AHI, with improvement in SaO2 min. This procedure could be eventually considered as an option of treatment for obese OSAHS patients with significant tonsil hypertrophy when continuous positive air pressure therapy is not possible as the first choice of treatment.

Correlations between pulse oximetry and peak expiratory flow in acute asthma

Few studies are available concerning correlations between pulse oximetry and peak expiratory flow in children and adolescents with acute asthma. Although the Global Initiative for Asthma states that measurements of lung function and oximetry are critical for the assessment of patients, it is not clear if both methods should necessarily be included in their evaluation. Since there is a significant difference in cost between pulse oximetry equipment and peak expiratory flow devices, we determined whether clinical findings and peak expiratory flow measurements are sufficient to determine the severity of acute asthma. The present prospective observational study was carried out to determine if there is correlation between pulse oximetry and peak expiratory flow determination in 196 patients with acute asthma aged 4 to 15 years diagnosed according to the Global Initiative for Asthma criteria. Patients experiencing their first or second wheezing episode, with fever, related acute or chronic diseases, and unable to perform the peak expiratory flow maneuver were excluded. Measurements of peak expiratory flow and pulse oximetry were performed at admission and after 15 min of each inhaled salbutamol cycle. Correlations obtained by linear regression using the Pearson correlation coefficients (r) were 0.41 (P < 0.0001), 0.53 (P < 0.0001), 0.51 (P < 0.0001), and 0.61 (P < 0.0001) at admission and after the first, second and third cycles of salbutamol, respectively. These correlations showed that one measure cannot substitute the other (Pearson's coefficient <0.7), probably because they evaluate different aspects in the airways, suggesting that peak expiratory flow should not be used alone in the assessment of acute asthma in children and adolescents.

TNF-a and IL-10 levels in tracheobronchial lavage of ventilated preterm infants and subsequent lung function

The role of airway inflammation in ventilated preterm newborns and the risk factors associated with the development of chronic lung disease are not well understood. Our objective was to analyze the association of the airway inflammatory response in ventilated preterm infants by serial measurements of TNF-a and IL-10 in tracheobronchial lavage (TBL) with perinatal factors and lung function measured early in life. A series of TBL samples were collected from ventilated preterm infants (less than 32 weeks of gestational age) and concentrations of TNF-a and IL-10 were measured by ELISA. Pulmonary function tests were performed after discharge by the raised volume rapid compression technique. Twenty-five subjects were recruited and 70 TBL samples were obtained. There was a significant positive association between TNF-a and IL-10 levels and length of time between the rupture of the amniotic membranes and delivery (r = 0.65, P = 0.002, and r = 0.57, P < 0.001, respectively). Lung function was measured between 1 and 22 weeks of corrected age in 10 patients. Multivariable analysis with adjustment for differences in lung volume showed a significant negative association between TNF-a levels and forced expiratory flow (FEF50; r = -0.6; P = 0.04), FEF75 (r = -0.76; P = 0.02), FEF85 (r = -0.75; P = 0.03), FEF25-75 (-0.71; P = 0.02), and FEV0.5 (r = -0.39; P = 0.03). These data suggest that TNF-a levels in the airways during the first days of life were associated with subsequent lung function abnormalities measured weeks or months later.

Gastroesophageal reflux episodes in asthmatic patients and their temporal relation with sleep architecture

Gastroesophageal reflux (GER) is common in asthma patients and can contribute to sleep disruption. The aim of the present study was to determine the time-related distribution of GER events together with their impact on sleep in asthmatic subjects with GER disease symptoms. The inclusion criteria were: 18-65 years, controlled moderate to severe asthma and GER-compatible clinical evidence. The exclusion criteria were: chronic obstructive lung disease, smoking, infections of the upper airways, use of oral corticosteroids, other co-morbidities, pregnancy, sleep-related disorders, night-time shift work, and the use of substances with impact on sleep. Asthmatic patients with nocturnal symptoms were excluded. All-night polysomnography and esophageal pH monitoring were recorded simultaneously. Of the 147 subjects selected, 31 patients and 31 controls were included. Seventeen patients were classified as DeMeester positive and 14 as DeMeester negative. Both groups displayed similar outcomes when general variables were considered. Sleep stage modification one minute prior to GER was observed in the DeMeester-positive group. Awakening was the most frequent occurrence at GER onset and during the 1-min period preceding 38% of the nocturnal GER. Sleep stage 2 was also prevalent and preceded 36% of GER events. In the DeMeester-negative group, awakening was the most frequent response before and during GER. Modifications in sleep stages, arousals or awakenings were associated with 75% of the total GER events analyzed during the period of one minute before and after the fall of esophageal pH below 4 in the DeMeester-positive group. These data provide evidence that sleep modifications precede the GER events in asthmatic patients.

Asthma: where is it going?

Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Although our understanding of its pathophysiological mechanisms continues to evolve, the relative contributions of airway hyperresponsiveness and inflammation are still debated. The first mechanism identified as important for asthma was bronchial hyperresponsiveness. In a second step, asthma was recognized also as an inflammatory disease, with chronic inflammation inducing structural changes or remodeling. However, persistence of airway dysfunction despite inflammatory control is observed in chronic severe asthma of both adults and children. More recently, a potential role for epithelial-mesenchymal communication or transition is emerging, with epithelial injury often resulting in a self-sustaining phenotype of wound repair modulation by activation/reactivation of the epithelial-mesenchymal trophic unit, suggesting that chronic asthma can be more than an inflammatory disease. It is noteworthy that the gene-environmental interactions critical for the development of a full asthma phenotype involve processes similar to those occurring in branching morphogenesis. In addition, a central role for airway smooth muscle in the pathogenesis of the disease has been explored, highlighting its secretory function as well as different intrinsic properties compared to normal subjects. These new concepts can potentially shed light on the mechanisms underlying some asthma phenotypes and improve our understanding of the disease in terms of the therapeutic strategies to be applied. How we understand asthma and its mechanisms along time will be the focus of this overview.

Advances in biliary atresia: from patient care to research

Biliary atresia, the most common cause of liver transplantation in children, remains a challenge for clinicians and investigators. The development of new therapeutic options, besides the typical hepatoportoenterostomy, depends on a greater understanding of its pathogenesis and how it relates to the clinical phenotypes at diagnosis and the rate of disease progression. In this review, we present a perspective of how recent research has advanced the understanding of the disease and has improved clinical care protocols. Molecular and morphological analyses at diagnosis point to the potential contributions of polymorphism in the CFC1 and VEGF genes to the pathogenesis of the disease, and to an association between the degree of bile duct proliferation and long-term outcome. In experimental models, cholangiocytes do not appear to have antigen-presenting properties despite a substantial innate and adaptive immune response that targets the biliary epithelium and produces duct obstruction. Initial clinical trials assessing the efficacy of corticosteroids in decreasing the inflammation and improving outcome do not show a superior effect of corticosteroids as an adjuvant treatment following hepatoportoenterostomy. The best outcome still remains linked to an early diagnosis and surgical treatment. In this regard, the Yellow Alert campaign by the Sociedade Brasileira de Pediatria and the inclusion of the Stool Color Card in the health booklet given to every neonate in Brazil have the potential to decrease the age of diagnosis, shorten the time between diagnosis and surgical treatment, and improve the long-term outcome of children with this devastating disease.

Three-year follow-up study of respiratory and systemic manifestations of chronic obstructive pulmonary disease

Few studies show patient outcomes over time in chronic obstructive pulmonary disease (COPD). In the present study, we monitored forced expiratory volume in the first second (FEV1) and other manifestations of the disease over 3 years in 133 COPD patients (69% males, age = 65 ± 9 years, FEV1 = 59 ± 25%) evaluated at baseline. During follow-up, 15 patients (11%) died and 23 (17%) dropped out. Measurements for 95 (72%) COPD patients alive after 3 years were analyzed. FEV1, body mass index (BMI), 6-min walking distance (6MWD), Medical Research Council scale (MRC), Saint George’s Respiratory Questionnaire (SGRQ), Charlson Comorbidity index, and BODE index were obtained at baseline and after 3 years. At baseline, 17 patients (18%) presented mild, 39% moderate, 19% severe, and 24% very severe COPD. Predicted FEV1 % and BMI did not change over the period (P > 0.05). FEV1 in liters [1.25 (0.96-1.72) vs 1.26 (0.88-1.60) L; P < 0.001], 6MWD (438 ± 86 vs 412 ± 100 m; P < 0.001), MRC [1 (1-2) vs 2 (1-3); P = 0.002], Charlson index [3 (3-4) vs4 (3-5); P = 0.009], BODE index (2.2 ± 1.8 vs 2.6 ± 2.3; P = 0.008), and total SGRQ (42 ± 19 vs 44 ± 19%; P = 0.041) worsened after 3 years compared to baseline measurements. These data show that COPD patients deteriorated during the 3-year follow-up despite the fact that they had only minor modifications in airway obstruction and body composition. They support the need for comprehensive patient assessment to better identify disease progression.

Inactivation of capsaicin-sensitive nerves reduces pulmonary remodeling in guinea pigs with chronic allergic pulmonary inflammation

Pulmonary remodeling is an important feature of asthma physiopathology that can contribute to irreversible changes in lung function. Although neurokinins influence lung inflammation, their exact role in the extracellular matrix (ECM) remodeling remains to be determined. Our objective was to investigate whether inactivation of capsaicin-sensitive nerves modulates pulmonary ECM remodeling in animals with chronic lung inflammation. After 14 days of capsaicin (50 mg/kg, sc) or vehicle administration, male Hartley guinea pigs weighing 250-300 g were submitted to seven inhalations of increasing doses of ovalbumin (1, 2.5, and 5 mg/mL) or saline for 4 weeks. Seventy-two hours after the seventh inhalation, animals were anesthetized and mechanically ventilated and the lung mechanics and collagen and elastic fiber content in the airways, vessels and lung parenchyma were evaluated. Ovalbumin-exposed animals presented increasing collagen and elastic fiber content, respectively, in the airways (9.2 ± 0.9; 13.8 ± 1.2), vessels (19.8 ± 0.8; 13.4 ± 0.5) and lung parenchyma (9.2 ± 0.9; 13.8 ± 1.2) compared to control (P < 0.05). Capsaicin treatment reduced collagen and elastic fibers, respectively, in airways (1.7 ± 1.1; 7.9 ± 1.5), vessels (2.8 ± 1.1; 4.4 ± 1.1) and lung tissue (2.8 ± 1.1; 4.4 ± 1.1) of ovalbumin-exposed animals (P < 0.05). These findings were positively correlated with lung mechanical responses to antigenic challenge (P < 0.05). In conclusion, inactivation of capsaicin-sensitive nerve fibers reduces pulmonary remodeling, particularly collagen and elastic fibers, which contributes to the attenuation of pulmonary functional parameters.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Dynamic expression of desmin, α-SMA and TGF-β1 during hepatic fibrogenesis induced by selective bile duct ligation in young rats

We previously described a selective bile duct ligation model to elucidate the process of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary stenosis. Using this model, we identified changes in the expression of alpha smooth muscle actin (α-SMA) both in the obstructed parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the expression profiles of desmin and TGF-β1, molecules known to be involved in hepatic fibrogenesis, were unchanged when analyzed by semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms involved in the modulation of liver fibrosis in this experimental model are not fully understood. This study aimed to evaluate the molecular changes in an experimental model of selective bile duct ligation and to compare the gene expression changes observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar rats of both sexes and weaning age (21-23 days old) were used. The rats were separated into groups that were assessed 7 or 60 days after selective biliary duct ligation. The expression of desmin, α-SMA and TGF-β1 was examined in tissue from hepatic parenchyma with biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO), using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods were significantly different. The BO parenchyma had a more severe fibrogenic reaction, with increased α-SMA and TGF-β1 expression after 7 days. The WBO parenchyma presented a later, fibrotic response, with increased desmin expression 7 days after surgery and increased α-SMA 60 days after surgery. The qRT‐PCR technique was more sensitive to expression changes than the semiquantitative method.

β-Citronellol, an alcoholic monoterpene with inhibitory properties on the contractility of rat trachea

β-Citronellol is an alcoholic monoterpene found in essential oils such Cymbopogon citratus (a plant with antihypertensive properties). β-Citronellol can act against pathogenic microorganisms that affect airways and, in virtue of the popular use of β-citronellol-enriched essential oils in aromatherapy, we assessed its pharmacologic effects on the contractility of rat trachea. Contractions of isolated tracheal rings were recorded isometrically through a force transducer connected to a data-acquisition device. β-Citronellol relaxed sustained contractions induced by acetylcholine or high extracellular potassium, but half-maximal inhibitory concentrations (IC50) for K+-elicited stimuli were smaller than those for cholinergic contractions. It also inhibited contractions induced by electrical field stimulation or sodium orthovanadate with pharmacologic potency equivalent to that seen against acetylcholine-induced contractions. When contractions were evoked by selective recruitment of Ca2+ from the extracellular medium, β-citronellol preferentially inhibited contractions that involved voltage-operated (but not receptor-operated) pathways. β-Citronellol (but not verapamil) inhibited contractions induced by restoration of external Ca2+ levels after depleting internal Ca2+ stores with the concomitant presence of thapsigargin and recurrent challenge with acetylcholine. Treatment of tracheal rings with L-NAME, indomethacin or tetraethylammonium did not change the relaxing effects of β-citronellol. Inhibition of transient receptor potential vanilloid subtype 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1) receptors with selective antagonists caused no change in the effects of β-citronellol. In conclusion, β-citronellol exerted inhibitory effects on rat tracheal rings, with predominant effects on contractions that recruit Ca2+ inflow towards the cytosol by voltage-gated pathways, whereas it appears less active against contractions elicited by receptor-operated Ca2+ channels.

Clinical impact of Achromobacter xylosoxidans colonization/infection in patients with cystic fibrosis

The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans.