The tracheal system of the Common Wasp (Vespula vulgaris) - A micro-CT study.

X-ray micro-CT has been used to study the tracheal system of Pre and Post hibernation Queen wasps (Vespula vulgaris) and their workers. We have compared our findings in wasps with Snodgrass's description of the tracheal system of the honeybee as characterised by anatomical dissection. Our images, whilst broadly similar, identify the tracheal system as being considerably more complex than previously suggested. One of the 30 wasps imaged had a markedly different, previously undescribed tracheal system. Since completing this study, a large micro-CT study from the American Museum of Natural History (AMNH) has been published. This used different software (Slicer) and analysed 16bit digital data. We have compared our methods with that described in the AMNH publication, adopted their suggested nomenclature and have made recommendations for future studies.

Lumacaftor-ivacaftor in the treatment of cystic fibrosis: design, development and place in therapy.

Lumacaftor-ivacaftor is a combination of two small molecule therapies targeting the basic defect in cystic fibrosis (CF) at a cellular level. It is a precision medicine and its effects are specific to individuals with two copies of the p.Phe508del gene mutation. The drug combination works by restoring functioning CF transmembrane conductance regulator (CFTR) protein in cell surface membranes and was the first CFTR modulator licensed for the homozygous p.Phe508del genotype. The drug is a combination of a CFTR corrector and potentiator. Lumacaftor, the corrector, works by increasing the trafficking of CFTR proteins to the outer cell membrane. Ivacaftor, the potentiator, works by enabling the opening of what would otherwise be a dysfunctional chloride channel. In vivo lumacaftor-ivacaftor improves Phe508del-CFTR activity in airways, sweat ducts and intestine to approximately 10-20% of normal CFTR function with greater reductions in sweat chloride levels in children versus adults. Its use results in a modest improvement in lung function and a decreased rate of subsequent decline. Perhaps more importantly, those treated report increased levels of well-being and their rate of respiratory exacerbations is significantly improved. This review traces the development and use of this combination of CFTR modulators, the first licensed drug for treating the homozygous p.Phe508del CF genotype at the intracellular level by correcting the protein defect.

Impact of antibiotic treatment for pulmonary exacerbations on bacterial diversity in cystic fibrosis.

BACKGROUND: A diverse array of bacterial species is present in the CF airways, in addition to those recognised as clinically important. Here, we investigated the relative impact of antibiotics, used predominantly to target Pseudomonas aeruginosa during acute exacerbations, on other non-pseudomonal species. METHODS: The relative abundance of viable P. aeruginosa and non-pseudomonal species was determined in sputa from 12 adult CF subjects 21, 14, and 7 days prior to antibiotics, day 3 of treatment, the final day of treatment, and 10-14 days afterwards, by T-RFLP profiling. RESULTS: Overall, relative P. aeruginosa abundance increased during antibiotic therapy compared to other bacterial species; mean abundance pre-antibiotic 51.0±36.0% increasing to 71.3±30.4% during antibiotic (ANOVA: F(1,54)=5.16; P<0.027). Further, the number of non-pseudomonal species detected fell; pre-antibiotic 6.0±3.3 decreasing to 3.7±3.3 during treatment (ANOVA: F(1,66)=5.11; P<0.027). CONCLUSIONS: Antibiotic treatment directed at P. aeruginosa has an additional significant impact on non-pseudomonal, co-colonising species.

Use of 16S rRNA gene profiling by terminal restriction fragment length polymorphism analysis to compare bacterial communities in sputum and mouthwash samples from patients with cystic fibrosis.

The bacterial communities present in the oral cavity and the lungs of 19 adult cystic fibrosis (CF) patients were compared by using terminal restriction fragment length polymorphism analysis of 16S rRNA gene PCR products amplified from nucleic acids extracted directly from bacteria in clinical samples. Sputum samples were not found to be subject to profound contamination by oral cavity bacteria. Evidence of colonization of the CF lung by certain oral bacterial species was found.

Resolution of peanut allergy following bone marrow transplantation for primary immunodeficiency.

Peanut allergy is a severe and life-threatening form of food allergy. Treatments are being developed but the mainstays of current management remain avoidance of peanut and appropriate use of rescue medication. We report the case of a boy with peanut allergy who required a bone marrow transplant (BMT) for combined immunodeficiency. A food challenge, 2 years after transplant, showed that his peanut allergy had resolved. Allergic disorders constitute a form of immune deviation and while we do not advocate BMT as a treatment for peanut allergy, we believe this case provides an insight into the basic mechanisms involved in food allergy.

Falsely elevated serum tobramycin levels in a patient receiving nebulised tobramycin.

It is common when treating patients with respiratory exacerbations of cystic fibrosis to use both nebulised and intravenous antibiotics. Aminoglycoside drug levels are often measured from finger-prick blood samples. We describe a case of a 14-year-old girl treated simultaneously with IV and nebulised tobramycin in whom drug levels, measured from finger prick blood samples, were erroneously high due to finger contamination by the nebulised drug. Special precautions or direct venepuncture is essential when assessing antibiotic levels in such patients.

Somatizing disorders affecting the respiratory tract.

Respiratory disease in childhood is common but not all children presenting to the paediatrician have an underlying organic cause for their symptoms. This article reviews the spectrum of non-organic somatization disorders that might be encountered and advises about the diagnosis and treatment of habit cough, laryngeal dysfunction and hyperventilation.

Bronchoalveolar lavage.

Bronchoalveolar lavage is a technique for sampling the epithelial lining fluid of the respiratory tract. Analysis of cellular and non-cellular components of returned fluid has the potential to provide valuable information about airways inflammation. Because of the invasive nature of the investigation, there are few conditions for which repeat sampling can be justified. Bronchoalveolar lavage has been used to study immune mechanisms in cystic fibrosis, interstitial lung diseases and asthma. This article reviews the usefulness of BAL assessments for lung inflammation in paediatric practice.

Faecal elastase 1: a marker of exocrine pancreatic insufficiency in cystic fibrosis.

Pancreatic elastase 1 (E1), a digestive protease, is synthesized by the acinar cells of the pancreas. Using an enzyme-linked immunosorbent assay, we evaluated stool E1 levels in the following groups of patients. (a) Specimens submitted for occult blood examination from 20 adults, over 3 consecutive days, to assess the inter-day variability in E1 excretion. There were no symptoms suggestive of pancreatic insufficiency in this group. The mean E1 concentration over all samples was 457 micrograms E1/g stool (range 124-1683). The intra-assay variation was 6.4% (n = 14) and the inter-assay variation was 8.8% (n = 12). The mean intra-patient variation was 17%. (b) Cystic fibrosis (CF) patients. Eight patients had E1 levels in the reference range (> 200 micrograms E1/g stool). The remaining 25 patients had undetectable E1 levels. (c) A control group of children presenting with unexplained bronchiectasis and/or recurrent respiratory infections and no symptoms of pancreatic dysfunction. The mean E1 concentration in the group was 519 micrograms E1/g stool (range 139-1941). There was no significant difference in E1 concentrations between the two non-CF groups, nor between the pancreatic-sufficient CF patients when compared with both non-CF groups. There was a significant difference between the pancreatic-sufficient and -insufficient CF groups (P < 0.001) using the Mann Whitney U test. All fifteen CF patients who were delta F508 homozygotes had undetectable E1. It may be possible to relate CF genotype to the presence or absence of E1 and to the degree of pancreatic insufficiency. Measurement of faecal E1 in children with CF appears to differentiate them into a group of children with normal pancreatic function and a larger group with severe insufficiency.

A randomised controlled trial to assess the relative benefits of large volume spacers and nebulisers to treat acute asthma in hospital.

OBJECTIVES: To compare the clinical effectiveness, acceptability, and cost benefit of administering beta2 agonists by means of a metered dose inhaler and large volume spacer with conventional nebulisers to children admitted to hospital with acute asthma. METHODS: A randomised controlled trial was conducted over five months. Sixty one children older than 3 years admitted to a large teaching hospital and a district general hospital with acute asthma completed the study. Children received either 5 mg of salbutamol up to one hourly by jet nebuliser, or up to 10 puffs of salbutamol 100 microg by means of a metered dose inhaler and spacer up to one hourly. RESULTS: Median hospital stay was 40 hours in the nebuliser group and 36.5 hours in the spacer group. Asthma disability scores at two weeks after discharge were significantly improved in the spacer group. Drug costs were pound 14.62 less for each patient in the spacer group. CONCLUSIONS: Large volume spacers are an acceptable, cost effective alternative to nebulisers in treating children admitted with acute asthma, provided that the children can use the mouthpiece, and symptoms are not severe. Their use facilitates effective home treatment by parents, with subsequent reduction in morbidity and re-admission rates.

Colonic wall thickening is related to age and not dose of high strength pancreatin microspheres in children with cystic fibrosis.

OBJECTIVE: Colonic fibrosis causing stricture is a recently described complication in cystic fibrosis (CF). Studies have suggested that ultrasound evidence of bowel thickening predicts this complication and that it is prevalent among children receiving large doses of high-strength pancreatin preparations. We performed ultrasound studies on our patients to look for evidence of bowel wall thickening or early stricture. METHOD: Detailed colonic ultrasounds were carried out in 33 children with CF including 25 who had been receiving high-strength pancreatin (Creon 25,000) continuously for 3 years at the time of study. RESULTS: Median lipase intake was 19 330 U/kg/day (range 0-59 880 U/kg/day) and median protease intake was 387 U/kg/day (range 0-1170 U/kg/day). The combined thickness of mucosa, sub-mucosa and muscle layers was measured in ascending, transverse and descending colon using a 7.5 MHz transducer. Measurements were also made in nine healthy controls. There was no relationship between enzyme dosage and colon thickness but simple regression identified a significant relationship (P < 0.001) between age and maximum colon thickness in all three areas. The colon of CF children was up to 50% thicker than in controls. CONCLUSIONS: Thickening of the order described elsewhere did not occur among any of the children studied. The results suggest that the most important factor determining the thickness of the CF colon is age.

Diagnosis of cystic fibrosis: Indian perspective.

Cystic fibrosis (CF) is one of the common life limiting inherited diseases in Caucasian population. Recent reports suggest that the diagnosis of cystic fibrosis in Indian children is missed or delayed due to low index of suspicion. The diagnosis of cystic fibrosis is suspected by the typical clinical features and should be confirmed by doing sweat chloride estimation. If sweat test is not available, ancillary tests including blood electrolyte and acid base balance, airway microbiology, tests to identify pancreatic insufficiency and semen analysis for obstructive azoospermia in post pubertal boys should be carried out. Positive results of these tests make the suspicion very strong. A strongly suspected case should be treated as cystic fibrosis, but for giving a diagnosis of CF, sweat test should be done from the nearest centre where it is available. In the presence of typical clinical features with borderline sweat chloride values sweat test should be repeated 2-3 times and the child should be investigated for alternative diagnosis. In the absence of alternative diagnosis with consistently high or borderline sweat chloride values an attempt should be made to get tests for mutations.

Presence of domestic pets and respiratory symptoms in asthmatic children.

The allergens of domestic pets such as cats, dogs and birds, have been known to sensitive predisposed individuals. In Singapore, approximately 25% to 35% of our atopic populations are sensitised to cat, dog or bird feather allergens. It is not known, however, if the presence of such domestic pets would translate to higher rates of sensitisation, or more importantly, give rise to increased respiratory symptoms. This study evaluated the association between the presence of domestic pets at home and the prevalence of respiratory symptoms among asthmatic children in Singapore. The parents of 1517 doctor-diagnosed asthmatic children were interviewed using the American Thoracic Society-Division of Lung Diseases respiratory questionnaire. More than 20% were found to have domestic pets (cats, dogs or birds) at home. Of these, those with exposure to passive smoke in the home were excluded. A total of 188 current pet owners (cats, dogs and birds) were demographically-matched for sex, race and socio-economic status (type of housing) to those without pets, past or current. Compared to those without pets, asthmatic children with pets at home had a higher prevalence of coughing with cold [relative risk (RR) 1.30; 95% confidence interval (CI) 1.01 to 1.69]; wheezing with cold (RR 1.42; CI 1.07 to 1.90), wheezing with shortness of breath (RR 1.33; CI 1.00 to 1.82), exercise-induced wheezing (RR 1.68; CI 1.10 to 2.56); and increased phlegm production or congestion with cold (RR 1.38; CI 1.00 to 1.91). This study suggests that the presence of domestic pets increases the prevalence of respiratory symptoms in asthmatic children. Those with predisposition to these allergens should avoid having these pets in the home or take specific precautions in avoiding their allergens.

Inflammatory pseudotumor of the trachea in a ten-month-old infant.

Inflammatory pseudotumors occur through a non-neoplastic process that involves abnormal proliferation of spindle cells (myoblasts and fibroblasts) with an inflammatory cell infiltrate. Clinically, radiographically, and grossly these lesions mimic malignant neoplasms but are readily distinguished histologically. We report an infant who presented with an inflammatory pseudotumor of his trachea that caused severe stridor.

Dietary fibre and the occurrence of gut symptoms in cystic fibrosis.

OBJECTIVE: To evaluate the effect of currently recommended energy rich cystic fibrosis diets on fibre intake and to investigate the relationship between fibre intake and the occurrence of gut symptoms. METHOD: Prospective completion of non-weighed five day food diaries by 28 children with cystic fibrosis and comparison of mean daily fibre intake with age matched controls who did not have cystic fibrosis. Prospective completion of similar diaries to a total of 68 children with cystic fibrosis and comparison of fibre and lipase intake with the occurrence of gut symptoms. RESULTS: Mean daily fibre intake in children with cystic fibrosis was 7.00 g compared with 14.65 g in controls (p < 0.001). Mean daily fibre intake in eight patients troubled with moderate or severe abdominal pain was 0.144 g/kg. This was significantly lower (p < 0.01) than mean values for 22 patients with occasional but mild symptoms (0.249 g/kg) and 38 with no gut symptoms (0.312 g/kg). There was a trend towards higher pancreatic enzyme doses (lipase/kg/day) in children with abdominal pain. CONCLUSIONS: Currently recommended cystic fibrosis diets have a low fibre content. A low residue diet might be an important factor in the pathogenesis of gastrointestinal symptoms.