The correlation of adenosine challenge test results with subsequent clinical course among young children with suspected asthma: a retrospective cohort study.

AIM: Our aim was to evaluate the correlation of Adenosine monophosphate challenge test (AMP-PCW) results with the patients' subsequent clinical course. METHODS: We performed a 6-year retrospective cohort study of young children with suspected asthma who underwent AMP-PCW test. RESULTS: Fifty four children were included in the study (median age, 50.5 months; range, 26-90). AMP-PCW was positive in 35 (65%) children. During the 3-year follow-up period, among 22 of 35 patients in the positive AMP-PCW group and among 17 of 19 in the negative AMP-PCW group-prophylactic therapy was not changed. Prophylactic therapy was initiated or its dose was escalated in 12 of 13 (92.3%) of the children with a positive AMP-PCW test compared to none of the children with a negative challenge test (P < 0.001). Prophylactic therapy was discontinued in only one (7.6%) of the children with a positive test as compared to two (100%) of the children with a negative test (P < 0.001). There were significantly fewer severe asthma exacerbations during a 3-year follow-up period after the challenge test as compared to the preceding 3-year period both in children with a positive (from 34 to 9 total events, P = 0.01) or a negative challenge test (from 16 to 0 events P = 0.01). The severity of airway hyper responsiveness was found to associate with the number of severe asthma exacerbations (P = 0.04) and with a diagnosis of asthma during the following 3 years (P = 0.02). CONCLUSIONS: AMP-PCW test results correlates with the subsequent clinical course of young children with suspected asthma performing the test.

Factors Associated with Positive Adenosine Challenge Test in Young Children with Suspected Asthma.

Background: To investigate the predictive factors associated with positive adenosine monophosphate challenge using the auscultation method (AMP-PCW) test results. Methods: This is a prospective study of young children with suspected asthma who underwent AMP-PCW test. Patients with a positive AMP-PCW test were compared with those with a negative AMP-PCW. A multivariate logistic regression model was performed to identify the independent determinants of positive AMP-PCW. Results: A total of 159 patients completed the AMP-PCW test. The median age was 53 months. In total, 54.0% of patients had a positive AMP-PCW. The prevalence of atopic dermatitis and family history of asthma and allergy were significantly higher among the positive AMP-PCW group (P = 0.04, P = 0.02, and P = 0.007, respectively), as were the prevalences of elevated immunoglobulin E (IgE), peripheral blood eosinophils percentage (P = 0.003, P < 0.001, respectively), and number of emergency department (ED) visits/hospitalizations before AMP-PCW test (P = 0.006). A significant inverse correlation exists between peripheral blood eosinophils percentage and serum IgE levels with the AMP end-point concentrations (r = -0.302, P = 0.001, and r = -0.312, P = 0.001, respectively). In multivariate logistic regression model, peripheral blood eosinophils percentage, IgE levels, and the number of ED visits/hospitalizations before the AMP-PCW test were found as independent predictors for positive AMP-PCW test result. Conclusions: Our results suggest that bronchial responsiveness to AMP-PCW is related to proxy markers of airway inflammation (elevated eosinophils and IgE levels) and clinical exacerbation of asthma before the test. This may support the role of AMP-PCW in detecting inflammatory changes and monitoring their trend among young children with suspected asthma.

Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up.

A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy.

[Foreign body aspiration in children].

Foreign body (FB) aspiration occurs mainly in children under 3 years of age and is one of the most frequent causes of accidental death under 12 months of age. The increased risk of FB aspiration in children is due to the different structure of the pharynx and the upper airways compared to adults. In addition, children have an immature swallowing mechanism and they most commonly aspirate food stuffs. FB aspiration is usually a sudden and dramatic event when the child feels that he is suffocating or choking. After the acute event, the clinical presentation widely ranges from severe respiratory distress to the most minimal symptoms. Bronchoscopy is the best diagnostic and therapeutic modality for FB inhalation. Prevention and rapid diagnosis can be lifesaving. In 2010, the American Academy of Pediatrics published a position paper on prevention of FB aspiration. The association calls for more proactive preventative measures to protect children from FB aspiration and to prevent mortality and morbidity. These include: 1. Raising awareness of parents and caregivers to supervise children and create a safe environment for them. 2. Promoting legislation and enforcing regulations that will prevent dangerous products being sold for children. 3. Changing the design of products, especially food products and toys, that will reduce the risks of choking. In this overview we will show the principles of diagnosis of FB aspiration and a flow chart including when flexible or rigid bronchoscopy is required.

Natural history of five children with surfactant protein C mutations and interstitial lung disease.

Interstitial lung diseases in infants and children are uncommon and may be caused by specific inborn errors of surfactant metabolism. Five children with open lung biopsy diagnosed interstitial lung disease were followed (mean of 27.2 years) and evaluated for surfactant protein gene mutations. Four of the children were originally diagnosed as desquamative interstitial pneumonitis and one as chronic interstitial pneumonitis. All had good response to chloroquine or hydroxychloroquine treatment for periods of 7-38 months. Lung function tests, incremental exercise tests, and rentgenological studies were performed in the children. Surfactant protein gene mutations were searched in all the patients and in part of their families. Three of the patients, aged now 32, 29, and 37 years, feel well and have normal lung function, while two of the patients, both females, aged 28 and 37 years, conduct normal activities of daily living, have healthy children but have clinical, physiological and rentgenological evidence of restrictive lung disease. All five patients were found to have surfactant protein C gene (SFTPC) mutations, three of them with the most common mutation (p.I73T) and the other two with new mutations of surfactant protein C gene (p.I38F and p.V39L). We conclude that detection of surfactant protein mutations should be attempted in all children presenting with interstitial lung disease. Furthermore, treatment with hydroxychloroquine should be considered in children with SFTPC mutations. Prospective evaluation of hydroxychloroquine therapy in a greater number of patients is needed.

Predictive value of adenosine 5'-monophosphate challenge in preschool children for the diagnosis of asthma 5 years later.

We evaluated the predictive values of preschool bronchial challenge with nebulized adenosine 5'-monophosphate (AMP) using the auscultation method for having asthma 5 years later. Preschool AMP challenge had a high negative (90%) and a moderate positive (67%) predictive value for asthma 5 years later. Positive predictive value increased with the age at which the challenge was performed. The degree of preschool response to AMP was associated with the severity of asthma at school age.

Cardiac, lung, and brain thrombosis in a child with obstructive sleep apnea.

A 3-year-old boy with failure to thrive and severe adenotonsillar hypertrophy with a clinical presentation of prolonged obstructive sleep apnea (OSA), was referred to the emergency room due to severe respiratory distress and anasarca. Echocardiography revealed right heart failure, a cystic lesion in the right ventricle and severe pulmonary hypertension. D-dimer was elevated but spiral computerized tomography (CT) and lung scan did not show any perfusion defects. Excision of the cardiac lesion during open-heart surgery, lung biopsy, and adenotonsillectomy were performed. Pathological examination showed an intracadiac organized thrombus and eccentric intimal fibrosis of the pulmonary arteries-which is a pathognomonic of pulmonary arterial microemboli. Brain CT revealed vein thrombosis of the left sigmoid sinus. Blood tests for inherited thrombophilia were normal. Today, 5 years after adenotonsillectomy, the child is normally developed, completely asymptomatic, free of any medications, and has a normal echocardiography. This case report may indicate that prolonged OSA can be a procoagulant state which can cause severe cardiovascular morbidity in children.

A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery.

Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

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.

Synchronous airway lesions in laryngomalacia.

OBJECTIVE: Laryngomalacia is the most common cause of congenital stridor. Laryngomalacia may be associated with other structural and functional airway lesions. While previous studies suggested a 10-45% rate of synchronous airway lesions (SALs), the exact rate and it's clinical significance is unknown. The purpose of this study was to determine the prevalence of SALs below the glottic level in congenital laryngomalacia, and to investigate possible relations with other clinical findings. METHODS: A cohort of 228 infants with congenital stridor who underwent fiberoptic flexible bronchoscopy (FFB) was analyzed. Data was collected from the hospital records. All procedures were reevaluated from the video recordings. RESULTS: SALs below the vocal cords were observed in 7.5% of the case (17/228). The most common SAL was tracheal bronchus followed by tracheomalacia and stenosis of the left main bronchus. No correlation was found between the presence of a SAL below the vocal cords and any other medical condition except for neurodevelopmental disorders. Except for one patient, all cases with SAL did not have any clinical symptoms or signs that would have suggested an accompanying airway lesion. CONCLUSIONS: The rate of SALs in infants with congenital stridor due to laryngomalacia is low and most of the additional lesions are benign. The yield of discovering clinically significant SALs below the glottic level is low and the routine search for a synchronous lesion below the vocal cords should be questioned. Except for underlying neurodevelopmental problems, no clear risk factors for the existence of SALs were identified.

Effect of low altitude at the Dead Sea on exercise capacity and cardiopulmonary response to exercise in cystic fibrosis patients with moderate to severe lung disease.

Oxygen supplementation may improve exercise tolerance and the physiological response to exercise in cystic fibrosis (CF) patients. Elevated barometric pressure at low altitude is a simple means of increasing the quantity of inspired oxygen. Our objectives were to examine the effect of natural oxygen enrichment (at the Dead Sea, 396 m below sea level) on exercise capacity, and the physiological responses to maximal and submaximal exercise in CF patients. Patients were tested twice: at sea level (barometric pressure, 754 +/- 6 mmHg, mean +/- SD), and at the Dead Sea (barometric pressure, 791 +/- 3 mmHg), in a randomized crossover design. We studied 14 CF patients (6 females, 8 males), aged 15-45 years, with moderate to severe lung disease (mean forced expired volume in 1 sec = 50.0 +/- 11.2% predicted). Tests at each site included resting spirometry, anthropometry, a graded submaximal exercise test, a maximal exercise test on a treadmill, and a 6-min walk test. Tests were performed in identical order at both sites. Tests at the Dead Sea were performed 72 hr after arrival. No differences between sites were observed in lung function at rest. Peak oxygen consumption was significantly improved at the Dead Sea compared with sea level (1.68 +/- 0.73 vs. 1.57 +/- 0.74 l/min, respectively, P = 0.05), along with an improvement in the ventilatory equivalent for oxygen (41.2 +/- 6.3 vs. 46.1 +/- 7.1, respectively, P < 0.05). During submaximal exercise, blood oxygen saturation improved at the Dead Sea compared with sea level at all exercise intensities (P < 0.05). In conclusion, these results suggest that even a brief stay at the Dead Sea area may have physiological benefits for CF patients with moderate to severe lung disease.

Timing and nature of wheezing at the endpoint of a bronchial challenge in preschool children.

Bronchial reactivity to inhaled agents in preschool children can be undertaken by auscultating the lungs to detect wheezing, but there is a lack of information on when wheeze first appears at the endpoint of the challenge and on the acoustic characteristics of the wheeze. We recorded breath sounds continuously during tidal breathing inhalation challenges with adenosine 5'-monophosphate, using sensors attached over each upper lobe in 80 preschool children. In 35 children, the challenge was considered positive by a pediatrician who determined the endpoint by detecting wheeze on auscultation after an inhalation. Using acoustic analysis, we determined that the first wheeze appeared during the 2-min period of nebulization in 31% of positive challenges; it was unilateral in 37%, and only inspiratory in 46%. A running window of 6 sec was used to detect at least two wheezes without reference to phase of breathing, and this index had a sensitivity of 97.6% and specificity of 99.7% for determining the endpoint of a challenge. Detecting wheeze acoustically adds safety to the technique by enabling the challenge to be stopped earlier, while the lack of a need to document the phase of breathing simplifies the technique.

CT of hemangiomas of the upper airways in children.

OBJECTIVE: Hemangiomas of the airways in infants are commonly diagnosed at bronchoscopy performed for the investigation of stridor or other respiratory symptoms. Occasionally on bronchoscopy the appearances are atypical or the entire extent of the suspected hemangioma cannot be appreciated. We report on the clinical usefulness of dynamic contrast-enhanced CT in the evaluation of suspected hemangiomas of the airways in infants. CT findings of 11 infants who underwent investigation for a suspected airway hemangioma were correlated with bronchoscopic findings. CONCLUSION: Dynamic contrast-enhanced CT is a valuable noninvasive method for the evaluation of airway hemangiomas. Although it can be used to confirm the diagnosis in patients with equivocal findings on bronchoscopy, we believe that CT findings are specific enough that CT can be recommended as the primary method of establishing the diagnosis. Multiplanar reconstructions illustrate the location, extent, and degree of luminal narrowing and any involvement of adjacent tissues.

Familial concordance of phenotype and microbial variation among siblings with CF.

The clinical spectrum of cystic fibrosis (CF) is influenced by the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. However, variable courses of the disease were demonstrated among patients with identical genotypes. Since siblings share identical CFTR mutations and environmental factors, they can serve as a model to assess the effect of modifier genes on disease expression, and also to evaluate cross-infection. The aim of this study was to compare disease expression among siblings with CF. All sibling pairs treated at 7 CF centers in Israel were included in the study. Data were collected from patients' medical charts. Fifty families with at least 2 siblings were identified. As expected, the second-born sibling was diagnosed at an earlier age compared to the first-born. The mode of CF presentation at diagnosis showed significant familial concordance. In the families where the first sibling presented with gastrointestinal manifestations, 79% of the second siblings also presented with gastrointestinal manifestations. When gastrointestinal manifestations were absent in the first sibling, only 12% of the second siblings presented with gastrointestinal manifestations (P < 0.0001). Likewise, when the first sibling presented with respiratory symptoms, 60% of the second siblings presented with the similar symptoms. However, when the first sibling presented without respiratory symptoms, only 12% of the second siblings presented with respiratory symptoms (P < 0.001). Meconium ileus (MI) was present in 20 patients (21%). In 10 families where the first-born sibling had MI, 8 (80%) of the subsequent siblings had MI. On the other hand, in the 39 families where the first-born sibling did not have MI, only 2 (5%) subsequent siblings had MI (P < 0.001). Pancreatic insufficiency (PI) also had high familial concordance (P < 0.0001). Percentile growth for weights and heights and lung function (FVC, FEV(1), and FEF(25-75)) at ages 7 and 10 years were similar between siblings. P. aeruginosa grew from sputum in 89% of our study patients. When P. aeruginosa was isolated from the first-born patient, 91% of the second siblings were also positive for P. aeruginosa, whereas when the initial sibling was not a carrier of P. aeruginosa, only 50% of subsequent siblings were positive (P < 0.0001). This familial concordance was not observed for S. aureus. By contrast, the age of first isolation of P. aeruginosa and S. aureus was significantly earlier in the second sibling than in the first for the two bacteria: 10.3 +/- 5.1 vs. 7.3 +/- 5.2 years (P < 0.05) for P. aeruginosa, and 11.5 +/- 5.4 years vs. 6.8 +/- 5.1 years (P < 0.05) for S. aureus. CF siblings tend to share similar phenotypes that are not mutation-dependent. The lack of variability between siblings in mode of initial CF presentation, rates of MI, pulmonary function, and nutritional status supports the role of modifier genes in the determination of these factors.

The effect of montelukast on bronchial provocation tests and exhaled nitric oxide levels in asthmatic patients.

BACKGROUND: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established. OBJECTIVE: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5'-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics. METHODS: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5'-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period. RESULTS: Montelukast treatment resulted in a significant improvement in exercise tolerance: median delta FEV1 20.0% (range 0-50) prior to treatment vs. 15.0% (range 0-50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO following therapy: median NO 16.0 ppb (range 7-41) vs. 13.0 (range 4.8-26) (P = 0.016). No change was seen in baseline lung function tests (FEV1, MEF50) or in the bronchial responsiveness (PC20) for methacholine and adenosine-5'-monophosphate. CONCLUSIONS: This study demonstrates that the leukotriene antagonist montelukast-sodium reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Exhaled nitric oxide is age-dependent in asthma.

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (