Systematic Analysis of CCNO Variants in a Defined Population: Implications for Clinical Phenotype and Differential Diagnosis.

Reduced generation of multiple motile cilia (RGMC) is a novel chronic destructive airway disease within the group of mucociliary clearance disorders with only few cases reported. Mutations in two genes, CCNO and MCIDAS, have been identified as a cause of this disease, both leading to a greatly reduced number of cilia and causing impaired mucociliary clearance. This study was designed to identify the prevalence of CCNO mutations in Israel and further delineate the clinical characteristics of RGMC. We analyzed 170 families with mucociliary clearance disorders originating from Israel for mutations in CCNO and identified two novel mutations (c.165delC, p.Gly56Alafs*38; c.638T>C, p.Leu213Pro) and two known mutations in 15 individuals from 10 families (6% prevalence). Pathogenicity of the missense mutation (c.638T>C, p.Leu213Pro) was demonstrated by functional analyses in Xenopus. Combining these 15 patients with the previously reported CCNO case reports revealed rapid deterioration in lung function, an increased prevalence of hydrocephalus (10%) as well as increased female infertility (22%). Consistent with these findings, we demonstrate that CCNO expression is present in murine ependyma and fallopian tubes. CCNO is mutated more frequently than expected from the rare previous clinical case reports, leads to severe clinical manifestations, and should therefore be considered an important differential diagnosis of mucociliary clearance disorders.

Bronchodilator responsiveness in wheezy infants predicts continued early childhood respiratory morbidity.

OBJECTIVE: Spirometry including bronchodilator responsiveness is considered routine in the workup of asthma in older children. However, in wheezy infants the existence of bronchodilator responsiveness and its prognostic significance remain unclear. METHODS: Infants (< 2 years) with chronic or recurrent wheezing or coughing were evaluated by infant pulmonary function testing (PFT). Maximal expiratory flow at the point of functional residual capacity (V̇maxFRC) was measured before and 20 minutes after salbutamol administration. Only infants with an obstructive profile (V̇maxFRC < 80% predicted) were included. The infants were divided into two groups with regard to whether or not a response to salbutamol was observed on PFT. A response was defined as a mean V̇maxFRC after salbutamol administration exceeding the upper confidence interval limit of individual pre-bronchodilator V̇maxFRC measurements. Follow-up data was gathered after a mean of 2 years. MEASUREMENTS AND MAIN RESULTS: Sixty infants were included in the study of which 32 (53%) demonstrated responsiveness to bronchodilators. The infants in the responsive group had a significantly higher frequency of physician visits for wheezing than the non-responders (3.0 mean visits/yr vs. 1.5 respectively, P = 0.03), and had a higher likelihood of having received asthma medication in the last year of the follow-up period (84% vs. 50% respectively, RR: 1.68[1.10-2.56]). At the end of the follow-up period, more parents in the responsive group reported continued respiratory disease (71% vs. 22%, RR:3.21[1.30-7.95]). CONCLUSIONS: Bronchodilator responsiveness can be demonstrated by infant PFT in infants with recurrent wheezing and can predict increased respiratory morbidity until 3 years of age.

Decline in asthma prevalence and severity in Israel over a 10-year period.

BACKGROUND: The prevalence of asthma has increased in western countries towards the end of the last century, but recently seems to have stabilized. OBJECTIVE: To evaluate trends in the prevalence and severity of asthma that occurred in Israel over the past decade. METHODS: The medical records of 17-year-old boys, eligible for national service, between 1999 and 2008 were reviewed. National annual hospitalization and death rates for asthma were extracted. RESULTS: Three hundred thousand medical records were reviewed. During the study period, lifetime asthma prevalence decreased from 9.7 to 8.1% (p = 0.002). The point prevalence of moderate-to-severe and mild persistent asthma decreased significantly from 0.88 and 3.41% to 0.36 and 2.44%, respectively, during this period. The prevalence of intermittent asthma and asthma in clinical remission for more than 3 years did not change significantly. The annual hospitalization rate for asthma decreased from 13.0 to 7.5 per 10,000 population (p < 0.0001), whilst the annual death rate due to asthma decreased between 1999 and 2008 from 2.1 to 1.4 per 100,000 population (p = 0.003). CONCLUSIONS: The prevalence of asthma in Israeli teenage boys decreased significantly over the last decade. In addition, asthma hospitalization and asthma-related death rates in the total population also decreased.

[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.

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.

Lung function response to bronchodilator nebulization via hood in wheezy infants: a pilot study.

BACKGROUND: In infants, small volume nebulizers with a face mask are commonly used to facilitate aerosol therapy. However, infants may be disturbed by mask application, causing poor mask-to-face seal and thus reducing the dose delivered. OBJECTIVES: To compare lung function response to bronchodilator nebulization via two delivery devices: hood versus mask. METHODS: We studied 26 recurrently wheezy infants aged 45.8 weeks (95% confidence interval 39.6-52.0). Inhalations of 0.30 mg/kg salbutamol were administered in two alliqots 30 minutes apart using mask and hood in alternating order (M+H or H+M). Response to inhalations was measured by maximal expiratory flows at functional residual capacity (V'maxFRC) at 5 minute intervals after each dose, and area under the V'maxFRC curve (AUC) was documented. RESULTS: A small but significant response to salbutamol was observed following the second inhalation with V'maxFRC, improving by 31.7% (7.2-56.2, P (0.02) and AUC by 425% x min (-154, 1004; P < 0.02). The improvement following salbutamol was similar by both delivery modalities but with a small but significantly better response when H was used after M (P < 0.01). CONCLUSIONS: Nebulized salbutamol induced a variable but positive response in wheezy infants. Salbutamol via hood was as effective as conventional face mask delivery. Since it is simple and patient-friendly, it could replace the face mask method particularly with uncooperative infants.

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.

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.

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.

Feeding young infants with their head in upright position reduces respiratory and ear morbidity.

The influence of feeding position of the infant in the pathogenesis of ear and airway diseases has not been well established. We investigated the influence of instructing mothers to feed their 3-month old infants with their head in an upright position on ear and respiratory morbidity during a one-year follow-up. Mothers of 88 infants were instructed by trained nurses to feed their infants with their head in upright position (intervention group). The control group consisted of 75 mothers of infants of similar socioeconomic background who fed their infants without special instructions. Both groups were followed at Maternal-Child-Health clinics. Feeding position was evaluated at the beginning and the end of the twelve-month study, and parent reported morbidity data of both groups were evaluated at every 3-month's follow-up meeting. Infants from the intervention group were fed at a more upright head position. Parameters of parent reported morbidity evaluated as area under the curve were significantly lower in infants from the intervention group concerning ear diseases, respiratory diseases, prolonged fever episodes, need of bronchodilator inhalations and antibiotic courses compared to the control group. Instructing mothers to feed infants with their head in upright position was accompanied with less morbidity and treatment burden.

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.

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.

Co-morbidities and cognitive status in a cohort of teenagers with asthma.

BACKGROUND: There is limited data regarding co-morbidities and cognitive status of asthma during childhood and adolescence. The aim of the current study was to explore the presence of co-morbidities and cognitive status in a large cohort of teenagers with asthma. METHODS: The medical records of 314,897 consecutive 17-year-old males, undergoing comprehensive medical and cognitive evaluation prior to recruitment for military service, were reviewed. The prevalence of co-morbidities and a cognitive assessment in subjects with asthma were compared to those without asthma. Both a univariate and multivariate logistic regression analysis were performed. RESULTS: Active asthma was documented in 21,728 (6.9%) subjects: 3.3% were diagnosed with mild intermittent asthma, and 3.6% with persistent asthma. A significant positive correlation between a higher cognitive score and prevalence of asthma was found (P < 0.001), with a 55% increased prevalence of asthma in the subjects with the highest cognitive score compared to those with the lowest score. The following co-morbidities were significantly more prevalent in asthmatics compared to non-asthmatics: chronic rhinitis (35% vs. 5%), atopic dermatitis (2% vs. 0.4%), urticaria (1% vs. 0.3%), anaphylaxis (0.4% vs. 0.1%), chronic sinusitis (0.4% vs. 0.1%), overweight with body mass index (BMI) above 25 kg/m(2) (20% vs. 17%) and underweight with BMI less than 17 kg/m(2) (3.2% vs. 2.8%), irritable bowel syndrome (IBS) (1% vs. 0.5%), and thyroid disorders(0.4% vs. 0.2%). Chronic rhinitis and sinusitis, atopic dermatitis, IBS, and thyroid disorders were all significantly more prevalent in persistent compared to intermittent asthma (P < 0.001). CONCLUSIONS: In adolescence, a higher cognitive status was associated with a higher rate of asthma. Chronic rhinitis was the most prevalent co-morbidity and was found in one third of adolescent asthmatics. Other allergic diseases, chronic sinusitis, over and underweight, IBS, and thyroid disorders were also more prevalent in asthmatics. Pediatr Pulmonol. 2016; 51:901-907. © 2016 Wiley Periodicals, Inc.

Collecting clinical data in primary ciliary dyskinesia- challenges and opportunities.

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

Primary ciliary dyskinesia in Israel: Prevalence, clinical features, current diagnosis and management practices.

BACKGROUND: Primary Ciliary Dyskinesia (PCD) is rare and its features in Israel have not been described. AIMS: to assess prevalence utilizing state-of-the-art diagnostic techniques, and describe clinical features, diagnostic and management practices in Israel. METHODS: A national multicenter study from 2012 to 2013 recruited patients diagnosed or suspected of having PCD. Diagnosis was verified using: nasal Nitric Oxide (nNO); High-speed Video Microscope Analysis (HVMA); Transmission Electron Microscopy (TEM) of cilia; Immuno-fluorescence staining (IF) for ciliary proteins, and genetic analysis. RESULTS: Of the 203 patients recruited from 14 pediatric centers, 150 had a PCD diagnosis verified. Median age was 15.05y, with range 0.15-60.5y. PCD prevalence was 1:54,000 for the general population and 1:25,000 in children (5-14 y). For the non-Jewish (mainly Druze and Arab Moslem) compared to Jewish populations, prevalence was 1:16,500 and 1:139,000 respectively (p < 0.0001) and parental consanguinity was 85.4% and 21.9% respectively (p < 0.0001). Clinical features included bronchiectasis (88%), rhinitis (81%), recurrent pneumonia (78%), recurrent otitis (62%), neonatal pneumonia (60%) and situs inversus (42%). Prior diagnostic practices varied widely between centers with TEM assessed in 55% and abnormal in 61% of these. Management included antibiotics and airway clearance. Diagnostic verification revealed for 150 PCD patients: 81% nNO<233 ppb, 62% abnormal HVMA, 51% diagnostic TEM, 58% diagnostic IF and, 57% genetic diagnosis. CONCLUSIONS: PCD in Israel is rare, with comprehensive diagnostic tests showing prevalence in children similar to Europe. Prevalence was higher in non-Jews, associated with parental consanguinity. Diagnostic and management practices vary. Referral centers providing comprehensive diagnostic and care capabilities should be established.

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.

Short-term acupuncture therapy is of no benefit in patients with moderate persistent asthma.

STUDY OBJECTIVES: Acupuncture traditionally has been used to treat asthma. Nevertheless, only a few controlled studies have been performed to determine the efficacy of this treatment. Our study aimed to determine the efficacy of acupuncture in patients with moderate persistent asthma. METHODS: Twenty-three patients with moderate persistent asthma who had been treated only with inhaled beta(2)-agonists were randomly assigned to receive four sessions of real acupuncture (RA) or sham acupuncture (SA) in a blinded manner. After a washout period of 3 weeks, the patients were crossed over. Monitoring included FEV(1), methacholine challenge, daily peak flow (PF) variability, and the keeping of an asthma diary. RESULTS: Twenty of 23 patients completed the study. There was no significant change in FEV(1) following treatment. The mean (+/- SE) FEV(1) values before and after the RA were 73 +/- 4% and 73 +/- 3%, respectively (not significant [NS]). FEV(1) values before and after SA were 70 +/- 3% and 70 +/- 3%, respectively (NS). There was also no change in provocative methacholine concentration causing a 20% fall in FEV(1) (PC(20)) before and after treatment. The mean PC(20) values before and after RA were 0.92 +/- 0.42 mg/mL and 1.16 +/- 0.51 mg/mL, respectively (p = 0.71), while the PC(20) values before and after SA were 1.47 +/- 0.83 mg/mL and 1.11 +/- 0.79 mg/mL, respectively (p = 0.59). There was no change in the mean PF variability before and after the RA (1.6 +/- 3.1% and 1.8 +/- 2.3%, respectively [NS]). The PF variability before and after SA were 3.6 +/- 2.8% and 2.8 +/- 3.4%, respectively (NS). No significant difference was demonstrated for symptom scores or for the use of beta(2)-agonist inhalers (RA, 6.7 +/- 3.4; SA, 8.1 +/- 3.6; p = 0.58). CONCLUSION: In patients with moderate persistent asthma, a short course of acupuncture treatment resulted in no change in lung functions, bronchial hyperreactivity, or patient symptoms.

Simple and specific test for the diagnosis of aspiration into the airways using a corn flour-milk mixture in a hamster model.

Aspiration into the airways is one of the major causes of lung disease in infants and young children. Unfortunately, the diagnosis of aspiration is often delayed due to unawareness and low sensitivity and specificity of existing diagnostic tests. We tested the efficacy of a new method, using a mixture of corn flour in milk instilled into the trachea, to diagnose aspiration in a hamster model. Forty-five female hamsters were used for the experiments. Twenty hamsters underwent tracheal instillation of 0.1 ml of a mixture of 7.5% corn flour (containing starch granules with a diameter of 2-30 microm) in milk. Twenty control animals underwent tracheal instillation of saline. Five hamsters served as naive controls. Five animals from the corn flour and saline groups underwent bronchoalveolar lavage on days 1, 3, 7, and 14 after tracheal instillation. Starch granules were identified under light microscopy, using both iodine and Diff-Quik staining in all the corn flour-instilled animals and during all days after tracheal instillation. No starch granules were detected in naive or saline-treated animals. Starch granules were detected over 14 days following tracheal instillation, with a half-life rate of disappearance of about 6 days. Corn flour aspiration in hamsters can be easily identified by light microscopy, using simple laboratory techniques.