Avraham Avital

Exercise but not methacholine differentiates asthma from chronic lung disease in children.

Bronchial provocation challenges with exercise and methacholine were performed on the same day or within a short interval in 52 children with asthma, 22 with other types of chronic lung disease (including cystic fibrosis), and 19 control subjects with no evidence of chronic lung disease. There were no significant differences in the baseline lung function before the two types of challenge in the individual groups and differences between the patients with asthma and with chronic lung disease were minor. When the mean -2 SD of the methacholine response of the control group was taken as the lower limit of normal, 49/52 (94%) patients with asthma and 18/22 (82%) with chronic lung disease responded abnormally. In contrast, with the mean +2 SD of the exercise response of the control group as the upper limit of normal, 41/52 (79%) asthmatic patients responded but none of those with chronic lung disease. Thus the response to the two types of challenge helps to distinguish asthma from other types of chronic lung disease in children.

Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial provocation tests.

Background: Bronchial provocation tests such as exercise, methacholine (MCH), and adenosine-5′-monophosphate (AMP) challenges are used extensively in the diagnosis of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO) can be used to diagnose asthma in patients with non-specific respiratory symptoms and to compare this test with conventional provocation tests. Methods: Patients with non-specific respiratory symptoms and normal spirometric parameters were included in the study. eNO was measured and exercise, MCH and AMP challenges performed in all subjects. Patients were defined as asthmatic based on clinical follow up 24 months after testing. Results: Forty patients were considered asthmatic and 45 were not. The area under receiver operating characteristic curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939 for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP respectively). From our data, a cut off value of NO >7 ppb at a flow rate of 250 ml/s best differentiates between asthmatics and non-asthmatics (sensitivity 82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise: ΔFEV1 ⩾10% (sensitivity 57.9%, specificity 100%); PC20-MCH: ⩽3 mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: ⩽150 mg/ml (sensitivity 89.5%, specificity 95.6%). Conclusions: Measurement of eNO can be used as a safe, simple and rapid test for the diagnosis of asthma and is as good as bronchial provocation tests.

MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia

Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS-encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus. MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO, when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC.

Yield from flexible bronchoscopy in children

Flexible fiberoptic (FO) bronchoscopy can now be undertaken readily in children using topical anesthesia and light sedation and has largely supplanted rigid open tube (OT) bronchoscopy for diagnostic purposes. The present study examined the contribution of the FO bronchoscope to clinical management in children presenting with specific types of problems. We examined the first 200 consecutive flexible bronchoscopies performed in 1995 in children under 18 years of age (median age, 2.27 years). Indications for bronchoscopy were noisy breathing (26.5%), recurrent pneumonia (21.0%), suspected pneumonia in an immunocompromised patient (10.5%), atelectasis or bronchial toilet (12.5%), possible foreign body aspiration (13.0%), and miscellaneous other reasons (16.5%). Inspection of the airway was abnormal in 67.0% of all investigations and made a clinically meaningful contribution to management in 67.5%, especially in those with noisy breathing (98.1%), possible foreign body aspiration (100%), and atelectasis (76.0%). Bronchoalveolar lavage (BAL) cytology was abnormal in 80.4% of the 107 lavages, but contributed little to management except in those with recurrent pneumonia (73.8%). Bacteria were isolated in 26.6% of the 109 specimens cultured, but this finding rarely affected management. Fungi were isolated in 47.4% of the 19 lavages in the immunocomprised group. Together, inspection, BAL and microbiology contributed to management in a mean of 90.5% (range, 76.2–100%) of patients in the various groups. We concluded that a high yield of clinically meaningful information can be expected from FO bronchoscopy in children when coupled with BAL and microbiological studies of lavage fluid. Pediatr. Pulmonol. 1997; 23:261–269

Amino-Terminal Pro-Brain-Type Natriuretic Peptide: Heart or Lung Disease in Pediatric Respiratory Distress?

Objectives. The aim of this study was to determine whether plasma levels of amino-terminal pro-brain natriuretic peptide (N-BNP) could differentiate between heart failure and lung disease among infants with acute respiratory distress. In addition, our aim was to determine whether plasma levels of N-BNP could be used to monitor the effects of treatment among infants with heart failure. Methods. Infants (age range: 1–36 months; median age: 10 months) who presented with respiratory distress underwent physical examination, plasma N-BNP measurement, and echocardiography within 24 hours after admission. Seventeen infants were finally diagnosed with acute heart failure and 18 with acute lung disease. Thirteen healthy infants served as a control group. Results. Plasma N-BNP levels were significantly higher for the infants with heart failure (median: 18452 pg/mL; range: 5375–99700 pg/mL) than for the infants with lung disease (median: 311 pg/mL; range: 76–1341 pg/mL). Among the infants with heart failure, there was a significant difference in plasma N-BNP levels before and after congestive heart failure treatment. Conclusion. Among infants with respiratory distress, plasma N-BNP measurements can differentiate between acute heart failure and lung disease and can be used to monitor the effects of treatment for infants with heart failure.

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each others results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.

Exercise, methacholine, and adenosine 5′-monophosphate challenges in children with asthma: Relation to severity of the disease

Bronchial hyperreactivity is a characteristic feature of asthma and can be evaluated by different challenges. The aim of this study was to compare exercise, methacholine (MCH), and adenosine 5′‐monophosphate (AMP) challenges in 135 children and young adults (mean age ± SD, 12.4 ± 3.9 years) with asthma, and to examine the utility of the different challenges in predicting those children with asthma likely to require prophylactic antiinflammatory treatment.

Home recording of PEF in young asthmatics: does it contribute to management?

The value of home monitoring of peak expiratory flow (PEF) as part of an action plan for asthma management in children and young adults is uncertain. We sought to determine whether home recording of PEF benefited asthma management and whether any contribution was affected by the severity of the asthma. Twenty-eight children and young adults with asthma of different severity (mean age 14 yrs; 95% confidence interval (95% CI) 12-16 yrs) recorded their symptoms, drug consumption and PEF twice daily for a mean of 82 days over a 12 week period, and attended the laboratory every 2 weeks for measurement of lung function. The number of individual patients with significant correlations for laboratory lung function tests compared with ambulatory PEF and diary scores averaged over the preceeding 2 weeks was low in all severity groups. When measured in the laboratory, PEF meter readings correlated poorly with PEF measured by spirometry. The proportion of patients with significant correlations for PEF, symptoms and rescue bronchodilator use on a day-to-day basis was 70-80% in the group of severe asthmatics and significantly less in the mild asthmatics. In a subgroup of 14 patients who were sick on a mean of 19 days, the mean difference in PEF between well and sick days was 14% of predicted. Diurnal PEF variation correlated poorly with other parameters in all groups. It is concluded that PEF monitoring adds little to daily recording of symptoms and bronchodilator use in the management of young patients with severe asthma, and it is too insensitive to register meaningful clinical changes in those with milder asthma.

Comparison of budesonide and beclomethasone dipropionate for treatment of asthma.

Beclomethasone dipropionate (BDP) and budesonide (BUD) were each given in a dose of 200 micrograms twice daily by metered dose inhaler to 10 asthmatic children already dependent on treatment with steroids. In a double blind randomised crossover study each course lasted one month. No clinically important differences were found between the two treatments when symptom scores, symptom free days, additional use of salbutamol, and results of lung function tests were considered. Metyrapone mildly reduced the plasma concentration of 11-deoxycortisol in two patients during treatment with budesonide, and in four during treatment with beclomethasone. It is concluded that although they are usually safe, both drugs may cause mild adrenal suppression when given in a dose of 200 micrograms twice daily.

Suspected Foreign Body Inhalation in Children: What Are the Indications for Bronchoscopy?

OBJECTIVE To define the criteria for bronchoscopy in children with suspected foreign body (FB) inhalation. STUDY DESIGN Health history, physical examination, and radiologic examination were performed before bronchoscopy in all children referred for suspected FB inhalation between 2003 and 2005. RESULTS A total of 142 children, ranging in age from 3 months to 14 years (median age, 20 months), were referred with a history of suspected FB inhalation. An FB was found in 42 children with abnormal physical and radiologic findings, in 17 children with abnormal physical or radiologic findings, and in 2 children with normal physical and radiologic finding but persistent cough. Bronchoscopy revealed no FB in the children with normal physical and radiologic examinations and no symptoms (n = 16). CONCLUSION In children with a history of choking, bronchoscopy is mandatory in the presence of persistent symptoms, such as cough, dyspnea, and fever, or any abnormal physical or chest radiography findings. Bronchoscopy is not necessary in asymptomatic children with normal physical and radiographic examinations.