Regular inhaled salbutamol : effect on airway responsiveness to methacholine and adenosine 5'-monophosphate and tolerance to bronchoprotection.

OBJECTIVE: Regular treatment with inhaled beta(2)-agonists increases airway responsiveness consistently to indirect bronchoconstrictors (allergen, exercise, hypertonic saline solution, etc) and inconsistently to direct bronchoconstrictors (histamine, methacholine). Studies demonstrating tolerance to beta(2)-agonist bronchoprotection against the indirect bronchoconstrictor adenosine 5'-monophosphate (AMP) have not examined changes in baseline AMP responsiveness. This study assessed the effect of regular salbutamol on AMP and methacholine responsiveness and on tolerance to bronchoprotection. DESIGN: Double-blind, randomized, crossover study. SETTING: University hospital bronchoprovocation laboratory. PATIENTS: Fourteen atopic asthmatic subjects with FEV(1) > 65% predicted, and methacholine provocative concentration causing a 20% fall in FEV(1) (PC(20)) < 8 mg/mL. INTERVENTIONS: Salbutamol, 100 microg, and placebo inhalers, two puffs qid, each for 10 days. MEASUREMENTS: Methacholine PC(20) and AMP PC(20) measured 12 h after blinded inhaler after each treatment period. Methacholine PC(20) and AMP PC(20) repeated 10 min after salbutamol, 200 microg (eight subjects). RESULTS: There was no difference between placebo and salbutamol treatment in geometric mean methacholine PC(20) (0.85 mg/mL vs 0.82 mg/mL, p = 0.86) or AMP PC(20) (22 mg/mL vs 17.4 mg/mL, p = 0.21; n = 14). The acute bronchoprotective effect of salbutamol was greater vs. AMP than vs methacholine (5.1 doubling concentrations vs. 3.5 doubling concentrations, p = 0.06) and loss of protective effect of salbutamol (mean +/- SD) was greater vs AMP than vs. methacholine (2.4 +/- 0.33 doubling concentration loss vs 0.8 +/- 0.21 doubling concentration loss, p = 0.008; n = 8). CONCLUSION: Regular salbutamol (mean +/- SD) treatment did not enhance airway responsiveness to either the indirect bronchoconstrictor AMP or the direct bronchoconstrictor methacholine. Compared to its effect on methacholine, salbutamol had a greater acute protective effect vs AMP and produced greater loss of protection vs AMP when used regularly.

Ventilatory responses to hypercapnia and hypoxia in relatives of patients with the obesity hypoventilation syndrome.

BACKGROUND: It is unclear why some morbidly obese individuals have waking alveolar hypoventilation while others with similar obesity do not. Some evidence suggests that patients with the obesity hypoventilation syndrome (OHS) may have a measurable premorbid impairment of ventilatory chemoresponsiveness. Such an impairment of ventilatory chemoresponsiveness in OHS, however, may be an acquired and reversible consequence of severe obstructive sleep apnoea (OSA). We hypothesised that, in patients with OHS who do not have coincident severe OSA, there may be a familial impairment in ventilatory responses to hypoxia and hypercapnia. METHODS: Sixteen first degree relatives of seven patients with OHS without severe OSA (mean (SD) age 40 (16) years, body mass index (BMI) 30 (6) kg/m(2)) and 16 subjects matched for age and BMI without OHS or OSA were studied. Selection criteria included normal arterial blood gas tensions and lung function tests and absence of sleep apnoea on overnight polysomnography. Ventilatory responses to isocapnic hypoxia and to hyperoxic hypercapnia were compared between the two groups. RESULTS: The slope of the ventilatory response to hypercapnia was similar in the relatives (mean 2.33 l/min/mm Hg) and in the control subjects (2.12 l/min/mm Hg), mean difference 0.2 l/min/mm Hg, 95% confidence interval (CI) for the difference -0.5 to 0.9 l/min/mm Hg, p=0.5. The hypoxic ventilatory response was also similar between the two groups (slope factor A: 379.1 l/min * mm Hg for relatives and 373.4 l/min * mm Hg for controls; mean difference 5.7 l/min * mm Hg; 95% CI -282 to 293 l/min * mm Hg, p=0.7; slope of the linear regression line of the fall in oxygen saturation and increase in minute ventilation: 2.01 l/min/% desaturation in relatives, 1.15 l/min/% desaturation in controls; mean difference 0. 5 l/min/% desaturation; 95% CI -1.7 to 0.7 l/min/% desaturation, p=0. 8). CONCLUSION: There is no evidence of impaired ventilatory chemoresponsiveness in first degree relatives of patients with OHS compared with age and BMI matched control subjects.

Protease inhibitor phenotype BsaskatoonM is not associated with emphysema - a 20-year follow-up study.

OBJECTIVE: To investigate the association between the PiBsaskatoon variant of alpha-1 protease inhibitor (a1 Pi), present in the heterozygous state, and the development of emphysema. DESIGN: Twenty-year follow-up in the third generation of a family with the variant, naturally controlled with regard to both environmental influences and other genetic factors. SETTING: University teaching hospital. POPULATION STUDIED: Ten siblings, five with PiBsaskatoonM phenotype and five with PiM phenotype, 33 to 46 years of age. INTERVENTIONS: Respiratory symptoms and smoking histories; pulmonary function tests, including static lung volumes, dynamic lung volumes before and after salbutamol 200 mg, and diffusing capacity; allergen prick skin tests; serum a1 Pi level, chest radiographs and high resolution computerized tomography lung scans MAIN RESULTS: The two groups of siblings had similar mean ages, smoking histories and prevalence of current mild respiratory symptoms. Pulmonary function data showed normal mean values and no statistically significant differences for all the variables between the two groups. Chest radiographs were normal in all subjects. High resolution computerized tomography scans were normal in eight subjects, and demonstrated mild and very mild centrilobular emphysema in the two subjects with greatest smoking histories (approximately 30 pack-year each); both of these were PiBsaskatoonM phenotype. CONCLUSION: There is no evidence of an association between a1 Pi phenotype PiBsaskatoonM and the development of emphysema.

Effect of high versus low ambient humidity on the severity of obstructive sleep apnoea.

BACKGROUND: Surface tension forces appear to make a significant contribution to upper airway closure in patients with obstructive sleep apnoea (OSA). It is possible that drying of the upper airway mucosa at night might contribute to these surface tension forces and the severity of OSA might therefore change with alteration of the ambient humidity. METHODS: A randomised single blind crossover study of high ambient relative humidity (HRH) versus low ambient relative humidity (LRH) was performed in 12 men of mean (SD) age 49 (9) years with mild OSA (apnoea/hypopnoea index (AHI) 14 (5.2)). On one night patients slept in continuous HRH (85 (4)%, range 80-93%) and on the other in LRH (16 (4)%, range 11-22%). RESULTS: The AHI was similar on the HRH and LRH nights (mean difference 3; 95% CI -2 to 9, p = 0.20 and no statistically significant differences in AHI were observed on the two nights after standardising for body position and sleep stage. Sleep stage distribution and the proportion of time spent in the supine position were similar on the HRH and LRH nights. The number of non-respiratory arousals was also similar on the two nights. CONCLUSION: Altering ambient humidity alone has no significant impact on the severity of OSA.

Positional treatment vs continuous positive airway pressure in patients with positional obstructive sleep apnea syndrome.

OBJECTIVES: The aim of this study was to compare the relative efficacy of continuous positive airway pressure (CPAP) and positional treatment in the management of positional obstructive sleep apnea (OSA), using objective outcome measures. DESIGN: A prospective, randomized, single blind crossover comparison of CPAP and positional treatment for 2 weeks each. SETTING: A university teaching hospital. PATIENTS: Thirteen patients with positional OSA, aged (mean+/-SD) 51+/-9 years, with an apnea-hypopnea index (AHI) of 17+/-8. MEASUREMENTS: (1) Daily Epworth Sleepiness Scale scores; (2) overnight polysomnography, an objective assessment of sleep quality and AHI; (3) maintenance of wakefulness testing; (4) psychometric test battery; (5) mood scales; (6) quality-of-life questionnaires; and (7) individual patient's treatment preference. RESULTS: Positional treatment was highly effective in reducing time spent supine (median, 0; range, 0 to 32 min). The AHI was lower (mean difference, 6.1; 95% confidence interval [CI], 2 to 10.2; p = 0.007), and the minimum oxygen saturation was higher (4%; 95% CI, 1% to 8%; p = 0.02) on CPAP as compared with positional treatment. There was no significant difference, however, in sleep architecture, Epworth Sleepiness Scale scores, maintenance of wakefulness testing sleep latency, psychometric test performance, mood scales, or quality-of-life measures. CONCLUSION: Positional treatment and CPAP have similar efficacy in the treatment of patients with positional OSA.

Continuous positive airway pressure requirement during the first month of treatment in patients with severe obstructive sleep apnea.

OBJECTIVES: (1) To compare the continuous positive airway pressure (CPAP) requirement at the time of diagnosis (T0), after 2 weeks (T2), and after 4 weeks (T4) of CPAP treatment, in patients with severe obstructive sleep apnea (OSA); and (2) to assess whether any alteration in CPAP requirement over the first 4 weeks of CPAP treatment would influence daytime alertness, subjective sleepiness, or mood. DESIGN: A prospective, controlled, single-blind crossover study. SETTING: University teaching hospital. PATIENTS: Ten patients with newly diagnosed and previously untreated severe OSA (aged 52+/-9 years, apnea hypopnea index [AHI] of 99+/-31) and subsequently 10 control patients (aged 52+/-11 years, AHI 85+/-17). MEASUREMENTS: Overnight polysomnography with CPAP titration to determine the CPAP requirement, which was standardized for body position and sleep stage, on all three occasions (T0, T2, T4). Objective sleep quality, daytime alertness, subjective sleepiness (Epworth Sleepiness Scale), and mood (Hospital Anxiety and Depression Scale). RESULTS: CPAP requirement decreased from T0 to T2 (median difference, 1.5 cm H2O, 95% confidence interval [CI], 1.1 to 2.7 cm H2O, p=0.0004) and did not differ between T2 and T4. Use of the lower CPAP pressure during T2 to T4 was associated with a decrease in Epworth scale (mean difference, 2.6, 95% CI, 1.2 to 4; p=0.01) and anxiety (median change, 2; 95% CI, 0.5 to 2.9, p=0.03) scores, as compared with the first 2 weeks. Daytime alertness did not differ between T0 to T2 and T2 to T4. CONCLUSION: CPAP requirement falls within 2 weeks of starting CPAP treatment. A change to the lower required CPAP was not associated with any deterioration in daytime alertness but was associated with small subjective improvements in sleepiness and mood.

[Inguinal herniotomy in prematurely born infants]. / Ingvinalna herniektomija kod prevremeno rodenog deteta.

INTRODUCTION: Inguinal hernia is the most common surgical condition in childhood; more than half of the cases occur during infancy (1, 2). As the number of surviving premature infants continues to grow, the pediatric surgeon has become more involved in the management of these hernias (3, 4). Several issues are contentious, such as the optimal time for herniotomy after diagnosis (5), the role of contralateral exploration, and the proper management for incarcerated inguinal hernia (6). Based on our experience, we attempted to study the above points in the infant population and we also examined the role of ventilator therapy in the etiology of inguinal hernia. MATERIAL AND METHODS: We performed a retrospective review of records of all infants under 6 months of age who underwent a repair of inguinal hernia at the Clinic for Pediatric Surgery in Novi Sad between January 1994 and December 1996. After surgery, all infants were included in a 6-week follow-up examination. RESULTS: During this period, 144 infants under 6 months of age underwent inguinal hernia repair. There were 114 males and 30 females. Fourteen patients had bilateral hernias at the time of presentation. Incarceration occurred in 32 infants (22%), that is in 27 of the 99 full-term cases (27%) and in 5 of the 45 preterm cases (11%). Only in three cases (8%) did it occur while the infant was awaiting repair. Over 90% of the full-term infants had their hernias repaired within 3 weeks from diagnosis. After reduction of incarceration, our policy is to operate within 24 to 48 hours. Four testicles appeared to be ischemic; one of these was excised. Patchy bowel ischemia was present in six cases, and bowel resection was required in one. The ovary and tube were twisted and ischemic at the time of operation, requiring oophorectomy in two female infants. Forty-five infants were premature. The mean age at the time of diagnosis was 8 weeks; at the time of herniotomy, it was 13 weeks. In the 24- to 28-week group, 44 of hernias were bilateral, and 7 of the 9 infants had been ventilated for an average of 6 weeks. The mean interval between diagnosis and surgery was 8 weeks for this group. DISCUSSION: The management of an apparently simple condition such as pediatric inguinal hernia can prove difficult. Deaths have occurred after complications or surgery for inguinal hernia, and most are probably avoidable (9). Morbidity is common and primarily related to incarceration or to damage to vas or testicular vessels during a difficult herniotomy. Because of our policy to operate within 3 weeks from diagnosis, only 8% of incarcerations occurred in infants known to have inguinal hernia. It is surprising that 35% to 41% of incarcerations repeatedly occur in already diagnosed cases (10, 11). Our policy of operating within 24 to 48 hours of manual reduction of incarceration would avoid the 40% reincarceration rate still being reported (6, 10). Our recurrence rate of 2% (3 cases) in comparison to that of other reports (5.4%) (12) we consider acceptable. Because only 5% of cases developed a contralateral hernia, the contralateral exploration is unnecessary. Testicular atrophy has been reported in 1%, even after routine herniotomy (13). There was a large number of premature infants (31%) in our series; the typical range is 9% to 21% (1, 4). The incidence of bilaterality (44%) in this group is very high. The explanation could be that hernias may be caused by ventilation-induced positive intraabdominal pressure, which keeps the processus vaginalis open. Contrary to contemporary belief (1), we found that incarceration is less common in preterm (11%) than in full-term infants (27%). CONCLUSION: The waiting period for premature infants is not hazardous, and herniotomy can be safely performed once the baby is mature (gestational age of 38 to 40 weeks), weighing more than 2200 grams, and is ready for discharge from the neonatal unit.

Surface tension forces in sleep apnea: the role of a soft tissue lubricant: a randomized double-blind, placebo-controlled trial.

Upper airway obstruction in patients with sleep apnea may occur in the absence of a negative intraluminal upper airway pressure. We hypothesized that surface tension forces may play a role in the pathogenesis of obstructive sleep apnea (OSA), and that a topical soft tissue lubricant might reduce the severity of OSA. Ten male patients (age 49 +/- 10 yr [mean +/- SD]; body mass index [BMI] 31 +/- 5 kg/m2) with OSA (apnea-hypopnea index [AHI] 17 +/- 9) were studied. The arousal index was lower with the lubricant treatment than with placebo (mean difference 8; 95% CI 4 to 11 arousals/h; p = 0.001). The AHI was lower, in each of the 10 patients, on the lubricant treatment than the placebo (mean change 10, 95% CI 6 to 13; p = 0.0003). The lower AHI with lubricant as compared with placebo was present in both supine (mean difference 13; 95% CI 5 to 20; p = 0.006) and nonsupine (mean difference 6; 95% CI 0 to 12; p = 0.05) positions. There was no significant difference in sleep architecture between the lubricant and placebo treatments. Application of a topical lubricant consistently reduced the severity of OSA. This implies a pathogenetic role for surface tension forces in OSA, and a potential role for surface tension-reducing agents in the treatment of OSA.

The current dilemma with spirometric inclusion criteria for asthma drug trials.

BACKGROUND: Spirometric inclusion criteria for asthma drug studies often require resting airflow obstruction and resting bronchoconstriction. By current standards, these criteria define suboptimal to poor asthma control. OBJECTIVE: To determine what proportion of asthmatic patients attending a tertiary University-based respiratory clinic meet typical drug study spirometric criteria of a baseline FEV1 of 50% to 80% predicted and > or = 15% delta FEV1 improvement following 200 micrograms inhaled albuterol. METHODS: A retrospective review was performed on charts of white caucasian asthmatic patients attending three respiratory physician outpatient clinics at a University-based tertiary referral center. We reviewed charts of all patients with chronic asthma under current therapy. We excluded subjects with additional lung diseases that might affect lung function. Spirometric data were extracted from the most recent scheduled outpatient visit. RESULTS: We reviewed 590 charts of patients with mean age 35.3 +/- 18.3 years (range 6 to 94), 43% male, and 50% atopic. There was objective evidence of variable airflow obstruction or airway hyperresponsiveness in 70.2%; the diagnosis of asthma was based on historical data alone in 29.8%. The majority of patients (87.5%) required inhaled corticosteroids with more than 50% using medium to high doses. Baseline FEV1 was > 80% in 84.6% of subjects, 50% to 80% in 14.4%, and < 50% in 1.0%. FEV1 improved by > or = 15% 10 to 15 minutes after 200 micrograms inhaled albuterol in 13.6%. Only 9.0% of the 590 asthmatic patients fulfilled both criteria (FEV1 50% to 80% and delta FEV1 > or = 15%). CONCLUSION: Less than 10% of asthmatic patients attending a tertiary referral respiratory clinic fulfilled typical spirometry inclusion criteria for asthma drug trials. We suggest this approach to enrollment in asthma drug studies be reevaluated.

Obstructive lung disease and sleep.

There is a significant interaction between obstructive lung disease and sleep--sleep is associated with clinical deterioration in obstructive lung disease, and vice versa. Knowledge of the pathophysiology of deterioration in obstructive lung disease during sleep is essential to the understanding of the management of this problem. Recent information has helped to clarify this pathophysiology and has led to more aggressive treatment for deterioration of obstructive lung disease during sleep. Whether this newer and more aggressive treatment strategy improves survival or morbidity in these conditions is a challenge for future research.

[Undescended testes and paratesticular anomalies]. / Nespusten testis i paratestikularne anomalije.

In the field of developmental paratesticular anomalies there are numerous questions without answers. The goal of this paper is to give some information on embryology of normal and disturbed development parallely, as well as to describe the occurrence of certain anomalies with a special review on anomalies of epididymis and deferent ductus considering their importance in urology. Results and statistical data from our work have been reported.

[Treatment of post-traumatic hemarthroses of the knee and ankle in children using transcutaneous electric nerve stimulation]. / Lecenje posttraumatskog hemartrosa kolenog i skocnog zgloba u dece primenon transkutane elektricne nervne stimulacije.

TENS (transcutaneous electric nerve stimulation) was applied in 36 children with knee or ankle hemarthros. Pain was diminished after first or second treatment and completely disappeared at the end of the first or second day. Swelling usually disappeared in the interval between the third and seventh day. At the end of the treatment joint movement was significantly improved. In the control group who received only conventional conservative treatment (puncture, immobilization or inactivity, drugs) swelling and pain were still present after the seventh day and these patients needed additional physiotherapy for next seven days. We consider the TENS a method of choice in the treatment of posttraumatic hemarthros providing that treatment starts immediately after the injury and that it is continually applied during 3-5 days. The patients are advised to use crutches. It is a simple, painless method which is not combined with any additional treatment. Proteolytic ointments can increase and stimulate the therapeutic effects.