Subjective assessment vs computer analysis of wheezing in asthma.

To determine if wheezing is a reproducible clinical sign, we presented recorded breath sounds from asthmatic patients to four groups of health professionals: pediatric residents, nurses, pediatricians, and physiotherapists. Their subjective assessments included scores of wheezing severity and estimates of wheezing duration. All participants repeated the test at least two weeks later. Results were compared to computer aided spectral analysis of the recorded breath sounds. Interobserver and intraobserver variability fell somewhat between chance and total agreement. In contrast, the computer analysis allowed an objective and reproducible characterization of wheezing in asthma.

Nomenclature used by health care professionals to describe breath sounds in asthma.

We studied the spontaneous, uninstructed description by 40 health care professionals of breath sounds in asthmatic patients, and their use of lung sound terminology following current recommendations. Tape play-back auscultation of recorded tracheal and lung sounds was performed by ten observers in each group of residents, nurses, staff physicians and physiotherapists. They repeated the test after two weeks to three months. Individual descriptions were compared to computer-aided characterization of the breath sound recordings. We found significant differences in the preferred terms for description of adventitious lung sounds between the groups of health care professionals. There was considerable intraobserver variability, with less agreement when suggestions for a more complex characterization were followed. Our observations indicate the importance of teaching a standardized nomenclature for lung sounds to health care professionals, using only terms which are clearly informative of pulmonary disease.

Normal lung growth following antenatal dexamethasone treatment for respiratory distress syndrome.

Antenatal steroid therapy reduces the incidence of respiratory distress syndrome (RDS) in premature infants. However, animal studies showed a decrease in lung cell number and lower lung weights in fetal rabbits exposed to hydrocortisone. This prompted us to measure flows and lung volumes (by spirometry and helium-dilution method) in children greater than 6 years who were part of a study by the Collaborative Group on Antenatal Steroid Therapy. The effect of antenatal steroids on subsequent pulmonary function had not previously been studied. Of the 158 children originally enrolled before birth, a total of 8 dexamethasone (DEX)- and 11 placebo-treated children were still local residents and fulfilled the criteria of the study (gestational age, 28-34 weeks; DEX/placebo treatment 1-7 days before delivery). Mean heights and weights were normal with no significant differences between the groups. Pulmonary function tests showed no differences in lung volumes or expiratory flows between the children whose mothers had received antenatal DEX and those who had received placebo. These results indicate no adverse effect of antenatal DEX on subsequent lung volumes and expiratory flows in childhood.

Elastase alpha 1-proteinase inhibitor and lactoferrin concentrations in endotracheal aspirates of ventilated newborns.

Bacterial colonization of the tracheo-bronchial tree is common and an established risk factor for infection in ventilated newborns. Elastase, a highly active proteinase, and lactoferrin, an iron-binding protein and potential modulator of the inflammatory process, are both major constituents of either azurophilic or primary granules of neutrophilic granulocytes, released by activation of these cells during the inflammatory response. Since both elastase, complexed with its major inhibitor alpha 1-proteinase inhibitor (E alpha 1-Pl), and lactoferrin (Lf) are indicators of granulocyte activation during bacterial infection, they may indicate infectious inflammation at the tracheobronchial site. To study whether these substances in a single suction probe may serve this purpose, we obtained 82 tracheo-bronchial aspirates routinely from 16 ventilated newborns with a median gestational age of 31.5 (range, 25-39) weeks for laboratory analysis and bacterial cultures. Systemic inflammatory response by differential white blood cell count and C-reactive protein (CRP) was monitored simultaneously. The median E alpha 1-Pl level was significantly elevated in culture-positive aspirates (1,005 micrograms/L; range, less than 30-29,240 micrograms/L) in contrast to culture-negative samples (158 micrograms/L; range, less than 30-1,408 micrograms/L). In addition to a diagnostic sensitivity of 77%, E alpha 1-Pl offered a high specificity of 88%, a positive predictive value of 97%, and a negative predictive value of 73%. In contrast, median Lf concentration (10.6; range, 0.3-58.3 mg/L vs. 11.7; range, 1.6-158 mg/L) showed no correlation with culture results. Of the culture-positive aspirates 36% corresponded with systemic signs of an acute inflammatory response, such as elevated I/T-ratio and CRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of terfenadine on the response to exercise and cold air in asthma.

To assess the role of histamine as a mediator in the response to exercise and isocapnic hyperventilation of cold air (IHCA) in asthma, we studied nine asthmatic subjects, age 13 to 25 years. All had exercise induced asthma (EIA) and positive responses to IHCA. Baseline lung function was measured before standardized challenges with histamine, exercise and IHCA. On separate days, these tests were repeated 3 h after a single oral dose of 120 mg terfenadine (TF). Histamine responsiveness decreased significantly, with a provocative concentration, producing a greater than or equal to 20% fall in FEV1 (PC20), of 1.1 +/- 0.8 mg/ml (mean +/- SEM) before and 12.0 +/- 4.9 mg/ml after the antihistamine. EIA was significantly less after TF, with 53 +/- 5% mean maximal falls in FEV1 from baseline before, and 29 +/- 9% after treatment (P less than 0.01, paired t-test). In contrast, the effect of TF on the response to IHCA was insignificant, with mean maximal falls of 45 +/- 7% in FEV1 before, and 41 +/- 7% after treatment. There was a correlation between PC20 and lowest FEV1 (% predicted) for EIA (r = 0.56, P less than 0.05), but not for IHCA (r = 0.34, NS). This study indicates a role of histamine as a mediator in EIA but not in IHCA, supporting different mechanisms for both stimuli.

Home measurement of oxygen saturation during sleep in patients with cystic fibrosis.

Feasibility and reproducibility of home measurement of arterial oxygen saturation (SaO2) were evaluated in 14 clinically stable patients with cystic fibrosis (CF). Changes in SaO2 during sleep were compared to the clinical status and pulmonary function while awake to identify predictors of nocturnal oxyhemoglobin desaturation. Each patient was assessed by clinical score, spirometry, and arterial blood gas analysis within 72 hours of the overnight study. Eight patients were studied on more than one occasion to assess dependence of SaO2 on position and reproducibility of overnight studies. A pulse oximeter stored up to 8 hours of nocturnal SaO2 measurements in its memory. Off-line analysis of trend data provided the proportion of sleep with SaO2 less than 90% and less than 85%. We found that patients with daytime PaO2 less than 60 mm Hg spent greater than 80% of their sleep with SaO2 less than 90%, while those with PaO2 greater than 70 mm Hg spent less than 20% of the night with SaO2 less than 90%. Patients with daytime PaO2 of 67-70 mm Hg were desaturated to less than 90%, from 0 to 98% of the night. No consistent body position dependence of daytime SaO2 was found. Home measurement of SaO2 during sleep was reproducible, with a difference on two repeat occasions of 4% +/- 2 (mean +/- SEM) for %time with SaO2 less than 90% and 3% +/- 2 for %time with SaO2 less than 85%. The severity of hemoglobin desaturation during sleep could not be reliably predicted from clinical scores or awake pulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS)

[Obliterating bronchiolitis following measles]. / Obliterierende Bronchiolitis nach Masern.

We report the complex clinical course over 15 years in a child who at the age of 19 months developed patchy pneumonic infiltrates and bronchiolitis after measles. Chronic atelectasis led to resection of the right upper lung lobe. He developed bilateral bronchiectases, predominantly in the right lung. Ventilation/perfusion scans showed a major reduction of both ventilation and perfusion mainly on the right side. Early recognition of obliterative bronchiolitis is important in order to provide adequate supportive treatment of possible complications.

[A 13-year-old boy with a mild form of cystic fibrosis and heterozygote gene mutation for Delta F508]. / Ein 13jähriger Junge mit einer milden Form der zystischen Fibrose und heterozygoter Genmutation für Delta F508.

We report a 13-year old boy with a chronic pseudomonas bronchitis who was first diagnosed as having cystic fibrosis at this age because of an elevated sweat chloride employing pilocarpine-iontophoresis. He is heterozygote for the gene mutation Delta F508. We point out the often moderate course of illness in compound heterozygotes.

Myocardial fibrosis--a rare complication in patients with cystic fibrosis.

We report a 10-month-old male infant who was admitted to our hospital with a history of failure to thrive and bulky stools. On examination, he was dystrophic and had a protruding abdomen, but he was well oxygenated and his lungs were clear on auscultation. A tachycardia of 145 beats per min and radiological evidence of cardiomegaly indicated involvement of the heart, but an ECG failed to show signs of myocarditis or cardiac hypertrophy. An elevated sweat chloride concentration of 141 mEq/l confirmed the diagnosis of cystic fibrosis (CF). Molecular analysis revealed heterozygosity for the common mutation delta F508. He died unexpectedly of a sudden cardiac arrest 2 days later. Autopsy revealed scattered myocardial necrosis and fibrosis. Some 50 documented cases of myocardial fibrosis in infants with CF have been reported. Suggested causes such as malnourishment and hypovitaminosis remain speculative as systematic studies have yet to be done.

Effect of inhaled ipratropium bromide on the airway response to methacholine, histamine, and exercise in patients with mild bronchial asthma.

We studied the bronchodilator and protective potency of inhaled ipratropium bromide in 33 patients with mild bronchial asthma. Patients were divided into 3 groups with similar baseline lung function and similar degrees of bronchial hyperresponsiveness to participate in the methacholine (study I, n = 9), histamine (study II, n = 9), or exercise challenge tests (study III, n = 18). At each session, 80 micrograms ipratropium bromide or placebo were inhaled in a double-blind randomized fashion. After ipratropium bromide, the mean specific airway resistance (SRaw) decreased from 10.4 to 4.9 (study I, p less than 0.01), 9.3 to 5.4 (study II, p less than 0.05), or 7.8 to 5.1 cm H2O.s (study III, p less than 0.01), respectively. Mean methacholine provocation concentrations necessary to increase SRaw by 100% were 0.43 after placebo and 8.60 mg/ml after ipratropium bromide (p less than 0.01), the respective values after histamine challenges were 1.32 mg/ml after placebo and 2.25 mg/ml after ipratropium bromide (p less than 0.01). In the exercise challenges, the individual responses varied largely with a mean maximum percent increase in SRaw of 231% after placebo and 173% after ipratropium bromide pretreatment (p less than 0.05). Therefore, ipratropium bromide offers bronchodilation and protection against a variety of stimuli and should more often be considered as an effective and safe drug for asthma treatment.

Pulmonary function in children with homozygous alpha1-protease inhibitor deficiency.

UNLABELLED: Alpha1-protease inhibitor (alpha1-PI) deficiency is a well-recognized cause of emphysema in adults; however, the natural history of this disorder in children is unclear. Because of the paucity of data in the paediatric age group, we performed whole body plethysmography, spirometry, and diffusing capacity, in a cohort of 17 homozygous (PiZZ phenotype) children (9 females, 8 males; mean age +/- SEM 13.4 +/- 0.9, range 7-18 years) and in 17 normal schoolchildren (13.5 +/- 0.9, 7-18 years), using a matched-pair design. Blood was drawn for determination of serum alpha1-PI levels, PI phenotype, and standard biochemical tests of liver function. Among the PiZZ subjects, 12 were detected during diagnostic workup of prolonged neonatal icterus, and 5 by routine testing in paediatric patients. None had chronic respiratory symptoms except for an 18-year-old PiZZ girl with a history of recent onset of exertional dyspnoea. All were non-smokers. The Wilcoxon test was used for statistical analysis. As expected, serum alpha1-PI levels were lower in the PiZZ group (16% of the control value). A few patients had slight elevations of their liver enzymes. As for the pulmonary function parameters, differences between groups were not significant. Individual data showed no consistent abnormality in lung function except for signs of mild expiratory obstructive airway disease with hyperinflation (elevated TGV/TLC ratio) in the only symptomatic 18-year-old subject (0.63, control subject 0.49). This was unresponsive to bronchodilators. For her, augmentation therapy with intravenous infusion of alpha1-PI may be considered. CONCLUSION: Our study confirms the absence of pulmonary function abnormalities in the vast majority of children with homozygous alpha1-PI deficiency. Serial measurements of lung function may help to distinguish those individuals who require treatment with alpha1-PI from those who do not.

[Turkish infant with hypoelectrolytemia and metabolic alkalosis as the sole manifestations of a mild form of cystic fibrosis (mutation D110H)]. / Türkischer Säugling mit Hypoelektrolytämie und metabolischer Alkalose als alleinige Manifestation einer milden Form der zystischen Fibrose (Mutation D110H).

We report the history of an infant who presented with hypotonic dehydration and metabolic alkalosis, in whom the diagnosis of cystic fibrosis was made on the basis of investigations for rare cystic fibrosis mutations. Since no other signs and symptoms of the CF disease were present, the finding of the rare mutation D110H on exon 4 of the CFTR-gene was paramount in the delineation of his underlying illness. He is now thriving well with a daily oral substitution of 1-2 grams of sodium chloride. A mild variant of cystic fibrosis has to be considered in infants presenting with unexplained hypoelectrolytemia and metabolic alkalosis. Like in our child, typical signs and symptoms of cystic fibrosis like maldigestion may not be present. The search has to be extended into "mild" mutations of the disease like D110H which was found in our case.

Comparison of the effects of inhaled corticosteroids on the airway response to histamine, methacholine, hyperventilation, and sulfur dioxide in subjects with asthma.

To investigate whether inhaled steroids modulate the airway response to different bronchoconstrictive stimuli, we studied 25 subjects with mild asthma with a double-blind, noncrossover design to compare the effect of a 3-week treatment with salbutamol (0.2 mg, four times a day [q.i.d.]) and placebo (N = 11) to the effect of salbutamol (0.2 mg q.i.d.) and inhaled beclomethasone dipropionate (BDP, 0.5 mg q.i.d.) (N = 14). Airway response to histamine and methacholine was assessed as the provocative concentration (in milligrams per milliliter) necessary to increase the specific airway resistance (SRaw) (in centimeters of H2O times second) by 100% (PC100 SRaw). Airway response to hyperventilation of air and to hyperventilation of 0.75 ppm of sulfur dioxide (SO2) was determined as the provocative ventilation (in liters per minute) necessary to increase SRaw by 75% (PV75 SRaw). Challenges were performed on separate days before and after treatment, and salbutamol inhalation was withheld at least 6 hours before each challenge. Salbutamol and placebo did not change perchallenge baseline SRaw nor did they have any significant effect on the airway response to the stimuli. Salbutamol and BDP decreased the mean prechallenge baseline SRaw (SEM) from 7.7 (0.37) to 5.9 (0.28) (p less than 0.01) and significantly (p less than 0.01) increased geometric mean (SEM) PC100 SRaw for histamine from 0.5 (1.42) to 0.9 (1.53) mg/ml; for methacholine, from 0.2 (1.47) to 0.5 (1.51) mg/ml; and mean (SEM) PV75 SRaw for hyperventilation of air from 51.8 (2.32) to 58.4 (1.86) L/min. In contrast, the change of PV75 SRaw during hyperventilation of SO2 from 26.2 (2.29) to 31.4 (3.30) L/min was not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prognosis of bronchial asthma in childhood]. / Die Prognose des Asthma bronchiale im Kindesalter.

The prevalence of childhood asthma is about 10% as compared to 6% in adults. 40% to 80% of asthmatic children become symptom-free during adolescence, but asymptomatic bronchial hyperreactivity may persist. About one third of those patients who have become symptom-free during adolescence will have relapses in adult life. Some factors seem to predict a worse prognosis of the disease: positive family history, concomitant allergic diseases, eczema, severe symptoms at the onset of the disease and during adolescence, a high degree of non-specific bronchial hyperreactivity, active and passive smoking. Questionable prognostic factors include sex, age of onset and breast-feeding.

[The effect of ipratropium bromide on lung function in patients with cystic fibrosis]. / Der Einfluss von Ipratropiumbromid auf die Lungenfunktion bei Patienten mit zystischer Fibrose.

The main manifestation of cystic fibrosis (CF) of the lungs is an obstructive ventilation disturbance. The fact that the administration of atropine improves pulmonary function in patients with CF suggests a vagal mechanism for the development of bronchal obstruction. In a single-blind, placebo-controlled study, we investigated the effect of 250 micrograms of an inhalation solution of the anticholinergic substance ipatropium bromide (IB) on the pulmonary function of 11 patients with CF (age range: 8 to 29 years). The mean figures for the changes in FEV1.0, FEF25-75%, RV and TLC after inhalation of IB and placebo did not differ significantly. However, FEV1.0 and FEF25-75% after administration of IB increased in 4 out of 11 patients, and decreased in one. The lung volumes changed significantly in only a single case. This variable effect of inhaled IB in CF patients is in agreement with findings that have been observed for other substances with a "bronchodilatory" effect in patients with CF.