João Terra-Filho

Frequency, Clinical Characteristics, and Respiratory Parameters of Hepatopulmonary Syndrome

OBJECTIVES To determine the frequency and the clinical characteristics of hepatopulmonary syndrome (HPS) in cirrhotic candidates for orthotopic liver transplantation and to identify the major respiratory parameters predictive of the presence of changes in arterial oxygenation. PATIENTS AND METHODS Patients underwent transthoracic contrast-enhanced echocardiography, pulmonary scintigraphy, pulmonary function test with diffusing capacity of lung for carbon monoxide (DLCO), and measurement of arterial blood gases. RESULTS Fifty-six patients were studied. Twenty-five patients (45%) presented with intrapulmonary vascular dilatations, but only 9 (16%) fulfilled the criteria for HPS. The clinical or demographic characteristics considered did not differ in the patients with and without HPS. The DLCO value was significantly lower in patients with HPS (P=.01). However, 32 (80%) of 40 patients with low DLCO values did not fulfill the criteria for HPS. An alveolar arterial oxygen gradient (AaPO2) of more than 20 mm Hg showed a higher diagnostic accuracy (91%) in the assessment of HPS than did the DLCO of less than 80% predicted (41%) and the AaPO2 of more than 15 mm Hg (71%). CONCLUSIONS The AaPO2 proved to be a more reliable index than PaO2 and DLCO for the determination of changes in arterial oxygenation in HPS. The DLCO does not seem to be a good marker for HPS screening. Intrapulmonary vascular dilatations were frequent, even in patients who did not fulfill the criteria for HPS.

Prevalence and risk factors for work-related asthma in young adults

Objectives: To investigate the prevalence and predictors of work related asthma in young adults from the general population. Methods: A total of 1922 subjects randomly selected from a birth cohort 1978/79 in Brazil, aged 23–25 years, completed a respiratory symptoms questionnaire based on the European Community Respiratory Health Survey, and underwent spirometry, bronchial challenge test with methacholine, and skin prick test. For subjects presenting with bronchial hyperresponsiveness, workplace exposure and its relationship with symptoms were assessed by a specific questionnaire and individualised job description to define cases of work related asthma. Results: The prevalence of work related asthma was 4.2% (81 cases): 1.5% (29 cases) were classified as aggravated asthma and 2.7% (52 cases) as occupational asthma. Work related asthma was associated with atopy and education. Lower educational level (1–8 years of schooling) was associated with work related asthma (odds ratio 7.06, 95% CI 3.25 to 15.33). There was no association between work related asthma and smoking, gender, or symptoms of rhinitis. Conclusion: The prevalence of work related asthma was high (4.2%), and was associated with low schooling, probably because of low socioeconomic level. The disease may therefore be a consequence of poverty.

Lung Function and Airway Hyperresponsiveness in Adult Patients with Sickle Cell Disease

Background:Lung disease is a major cause of morbidity and death in sickle cell disease. Although airway hyperresponsiveness has been noted in children, there are no studies in adult sickle cell patients. The aim of this study was to investigate the prevalence of airway hyperresponsiveness in adult sickle cell patients. Methods:Twenty-six patients with sickle cell disease (10 HbSC, 9 HbSS, and 7 HbSβ) were compared with 28 normal control subjects. Pulmonary function tests, including spirometry, measurements of single-breath diffusing capacity and the methacholine challenge test were performed. Results:There were no significant differences in age, gender, or height between groups. Restrictive ventilatory defect was observed in six patients (24%) in the sickle cell disease group. Obstructive ventilatory defect and reduced diffusing lung DLCO capacity was observed in all sickle cell disease subgroups. A positive methacholine challenge test was obtained in eight (31%) sickle cell patients and in two of the 28 controls (7%). Conclusion:These features suggest that there is a high prevalence of airway hyperresponsiveness in adult patients with sickle cell disease without a history of reactive airway disease.

Comparison of 4 AM and 4 PM Bronchial Responsiveness to Hypertonic Saline in Asthma

Bronchial responsiveness to methacholine or histamine increases at night and may contribute to the mechanisms of nocturnal asthma. Hypertonic saline (HS) is a more clinically relevant stimulus for the diagnosis and assessment of the severity of asthma, but the circadian variation in bronchial responsiveness to hypertonic challenges has not been addressed. The aim of this study was to compare the responsiveness to hypertonic saline at 4:00 AM and at 4:00 PM. Eighteen diurnally active patients (11 women) with asthma, 31 ± 9 years of age (mean ± SD) and with a forced expiratory volume in 1 s (FEV1) of 79.11% ± 12.85%, underwent two challenge tests (4:00 AM and 4:00 PM) in random sequence separated by an interval of 7 days. The challenge test consisted of inhalations of 4.5% saline with increasing doses by doubling the duration of nebulization (0.5, 1, 2, 4, and 8 min). The inhalation continued until a drop of 20% in FEV1 was achieved or total time of 15.5 min. The provocative dose that caused the 20% drop in FEV1 (PD20) was calculated. Differences were found between 4:00 PM and 4:00 AM values for inhalation times [3.80 ± 3.57 min and 2.19 ± 2.42 min (p = 0.001), respectively] and for PD20 [4.94 ± 6.77 ml and 2.93 ± 4.74 ml (p = 0.002), respectively]. Eight patients with a home-assessed nocturnal peak expiratory flow (PEF) drop of more than 15% formed the nocturnal asthma group. The behavior of these patients was similar to that of the non-nocturnal asthma group. We conclude that the bronchial responsiveness to HS increases at night.

Effects of intravenous atropine on static P-V curves of the lung in normal man

In eight normal subjects we studied the effects of intravenous (i.v.) injection of 2 mg atropine sulfate on the static lung recoil pressure-volume (PV) curves, plethysmographic airway resistance (Raw), and maximum expiratory flow rates (Vmax). In addition, we determined the influence of atropine injection in esophageal elastance (Ees) by measuring the esophageal pressure with an esophageal balloon containing five different volumes (0.5 to 4 ml) of air and by calculating the change in esophageal pressure per unit change in balloon volume (delta Pes/delta Vb). This procedure allowed us to obtain static lung recoil pressure (Pst(1] at a balloon volume extrapolated to zero, thus avoiding the interference of changes in esophageal tone following atropine administration with the measurement of Pst(1). After vagal blockade with atropine, Pst(1) significantly decreased with a shift to the left of PV curves, Raw decreased, and Vmax increased mainly at lower lung volumes. Ees also decreased with parasympathetic blockade. We interpret these findings to indicate that inhibition of vagal tone results in dilatation of large and small airways, and also in the relaxation of smooth muscle in terminal lung units.

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients

This prospective study analyzed the involvement of the autonomic nervous system in pulmonary and cardiac function by evaluating cardiovascular reflex and its correlation with pulmonary function abnormalities of type 2 diabetic patients. Diabetic patients (N = 17) and healthy subjects (N = 17) were evaluated by 1) pulmonary function tests including spirometry, He-dilution method, N2 washout test, and specific airway conductance (SGaw) determined by plethysmography before and after aerosol administration of atropine sulfate, and 2) autonomic cardiovascular activity by the passive tilting test and the magnitude of respiratory sinus arrhythmia (RSA). Basal heart rate was higher in the diabetic group (87.8 +/- 11.2 bpm; mean +/- SD) than in the control group (72.9 +/- 7.8 bpm, P<0.05). The increase of heart rate at 5 s of tilting was 11.8 +/- 6.5 bpm in diabetic patients and 17.6 +/- 6.2 bpm in the control group (P<0.05). Systemic arterial pressure and RSA analysis did not reveal significant differences between groups. Diabetes intragroup analysis revealed two behaviors: 10 patients with close to normal findings and 7 with significant abnormalities in terms of RSA, with the latter subgroup presenting one or more abnormalities in other tests and clear evidence of cardiovascular autonomic dysfunction. End-expiratory flows were significantly lower in diabetic patients than in the control group (P<0.05). Pulmonary function tests before and after atropine administration demonstrated comparable responses by both groups. Type 2 diabetic patients have cardiac autonomic dysfunction that is not associated with bronchomotor tone alterations, probably reflecting a less severe impairment than that of type 1 diabetes mellitus. Yet, a reduction of end-expiratory flow was detected.

Protective effect of bronchial challenge with hypertonic saline on nocturnal asthma

Inhalation of hypertonic saline (HS) causes bronchoconstriction in asthmatic subjects. Repeated inhalation of HS leads to substantially reduced bronchoconstriction, known as the refractory period. Refractoriness due to different stimuli has also been described (cross-refractoriness). Nocturnal asthma is defined as an increase in symptoms, need for medication, airway responsiveness, and/or worsening of lung function that usually occurs from 4 to 6 am. Our objective was to determine the effect of refractoriness on nocturnal asthma. The challenge test consisted of inhalations of 4.5% saline with increasing durations until a reduction of 20% in forced expiratory volume in 1 s (FEV1) (PD20HS) or total time of 15.5 min. Twelve subjects with nocturnal asthma were challenged with HS at 16:00 and 18:00 h and FEV1 was measured at 4:00 h. One to 2 weeks later, FEV1 was determined at 16:00 and 4:00 h. LogPD20HS at 18:00 h was significantly greater than logPD20HS at 16:00 h, 0.51 +/- 0.50 and 0.69 +/- 0.60 mg, respectively (P = 0.0033). When subjects underwent two HS challenges in the afternoon, mean (+/- SD) FEV1 reduction was 206 +/- 414 mL or 9.81 +/- 17.42%. On the control day (without challenge in the afternoon) FEV1 reduction was 523 +/- 308 mL or 22.75 +/- 15.40% (P = 0.021). Baseline FEV1 values did not differ significantly between the control and study days, 2.48 +/- 0.62 and 2.36 +/- 0.46 L, respectively. The refractory period following HS challenges reduces the nocturnal worsening of asthma. This new concept may provide beneficial applications to asthmatic patients.