Fluorescent nuclear track detectors for alpha radiation microdosimetry.

BACKGROUND: While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues. METHODS: Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival. RESULTS: The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (< 5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 - 51%). CONCLUSIONS: The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.

The therapeutic potential of polymersomes loaded with 225Ac evaluated in 2D and 3D in vitro glioma models.

Alpha emitters have great potential in targeted tumour therapy, especially in destroying micrometastases, due to their high linear energy transfer (LET). To prevent toxicity caused by recoiled daughter atoms in healthy tissue, alpha emitters like 225Ac can be encapsulated in polymeric nanocarriers (polymersomes), which are capable of retaining the daughter atoms to a large degree. In the translation to a (pre-)clinical setting, it is essential to evaluate their therapeutic potential. As multicellular tumour spheroids mimic a tumour microenvironment more closely than a two-dimensional cellular monolayer, this study has focussed on the interaction of the polymersomes with U87 human glioma spheroids. We have found that polymersomes distribute themselves throughout the spheroid after 4 days which, considering the long half-life of 225Ac (9.9 d) (Vaidyanathan and Zalutsky, 1996), allows for irradiation of the entire spheroid. A decrease in spheroidal growth has been observed upon the addition of only 0.1 kBq 225Ac, an effect which was more pronounced for the 225Ac in polymersomes than when only coupled to DTPA. At higher activities (5 kBq), the spheroids have been found to be destroyed completely after two days. We have thus demonstrated that 225Ac containing polymersomes effectively inhibit tumour spheroid growth, making them very promising candidates for future in vivo testing.

Alpha particle spectroscopy using FNTD and SIM super-resolution microscopy.

Structured illumination microscopy (SIM) for the imaging of alpha particle tracks in fluorescent nuclear track detectors (FNTD) was evaluated and compared to confocal laser scanning microscopy (CLSM). FNTDs were irradiated with an external alpha source and imaged using both methodologies. SIM imaging resulted in improved resolution, without increase in scan time. Alpha particle energy estimation based on the track length, direction and intensity produced results in good agreement with the expected alpha particle energy distribution. A pronounced difference was seen in the spatial scattering of alpha particles in the detectors, where SIM showed an almost 50% reduction compared to CLSM. The improved resolution of SIM allows for more detailed studies of the tracks induced by ionising particles. The combination of SIM and FNTDs for alpha radiation paves the way for affordable and fast alpha spectroscopy and dosimetry.

Long-term effects of birth order and age at diagnosis in cystic fibrosis: a sibling cohort study.

BACKGROUND: Siblings with cystic fibrosis (CF) share many genetic and environmental factors but may present different phenotypes. Younger sibs are mostly earlier diagnosed with CF than their older sibs, but might be at risk for an earlier colonization with Pseudomonas aeruginosa (PA) than their older counterparts due to cross-infection within families. AIMS: To analyze the effects of birth order and age at diagnosis on lung function, PA colonization, nutritional status, and survival during the first two decades of life in siblings with CF. METHODS: A retrospective cohort study of 52 sibling pairs was performed in two Dutch CF centers. Data were analyzed both cross-sectionally and longitudinally using Kaplan-Meier curves and modified log-rank tests. RESULTS: Median age at diagnosis was significantly higher in the older sib compared with the younger sib (3.0 and 0.2 years, respectively, P < 0.0001). At the age of 5, 10, and 15 years no difference in lung function was found. However, at the age of 20 years, forced expiratory volume in 1 sec (FEV(1)) in older sibs was 19.4% (95% CI: 5.9-32.9%, P = 0.007) lower than in younger sibs. In the younger sibs group, FEV(1) at age 20 years was significantly better in those who had a diagnosis before the age of 6 months (difference 22.9%, 95% CI: 0.1-45.8%, P < 0.05). In the first 10 years of life the younger sibs tended to be earlier colonized with PA than their older counterparts. No differences in nutritional status and survival were observed. CONCLUSION: In this sibling cohort study, an early diagnosis of CF was associated with better lung function after two decades of life. Although younger siblings tended to be colonized with PA at an earlier age, they showed better lung function outcomes. This underscores the importance of early diagnosis with newborn screening and early referral to a specialized center in the prevention of long-term deleterious effects on lung function.

Demographics of glucose metabolism in cystic fibrosis.

We investigated the prevalence of cystic fibrosis-related diabetes (CFRD) and its association with various demographic and clinical conditions in a Dutch child and adult cystic fibrosis (CF) population. Patients were classified as having either normal glucose tolerance (NGT), impaired glucose tolerance (IGT) or CFRD. Associations with the following parameters were studied: age, gender, BMI, mutations, pulmonary function, infection status, and hospitalization. In our patient population the prevalence of IGT and CFRD was 16% and 31% respectively. After excluding pancreatic sufficient patients, the prevalence of CFRD was 40% and in patients over 40 years 52%. Compared with patients with NGT, CFRD patients were older, had more in-hospital days and had worse pulmonary function. Women developed CFRD at a significantly younger age than men. CFRD is a frequently occurring co-morbidity in patients with CF. The prevalence of CFRD is increasing in ageing CF populations and deserves rising attention in CF management.

Recombinant human deoxyribonuclease for the treatment of acute asthma in children.

BACKGROUND: Airway obstruction in acute asthma is the result of airway smooth muscle contraction, inflammation and mucus plugging. Case reports suggest that mucolytic therapy might be beneficial in acute asthma. The aim of this study was to determine the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase) in addition to standard treatment at the emergency department in children with an asthma exacerbation. METHODS: In a multicentre randomised double-blind controlled clinical trial, 121 children brought to the emergency room for a moderate to severe asthma exacerbation were randomly assigned to receive either a single dose of 5 mg nebulised rhDNase or placebo following the second dose of bronchodilators. An asthma score (scale 5-15) was assessed at baseline and at 1, 2, 6, 12 and 24 h. The primary outcome variable was the asthma score 1 h after the study medication. RESULTS: One hour after the study medication the asthma score in the rhDNase group showed an adjusted mean decrease from baseline of 1.0 (95% CI 0.5 to 1.6) points compared with 0.7 (95% CI 0.3 to 1.2) points in the placebo group (mean difference 0.4 (95% CI -0.2 to 1.0) points; p = 0.23). The asthma score over the study period of 24 h also did not differ significantly between the rhDNase and placebo group (mean difference 0.2 (95% CI -0.3 to 0.7) points, p = 0.40). The duration of oxygen supplementation and number of bronchodilator treatments in the first 24 h were similar in both groups. CONCLUSION: Adding a single dose of nebulised rhDNase to standard treatment in the emergency room has no beneficial effects in children with moderate to severe acute asthma.

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

[Facial paresis in children; consider Lyme disease]. / Facialisparese bij kinderen; denk aan Lyme-ziekte.

Three girls, aged 3, 7 and 13 years, developed acute peripheral facial palsy. The first patient was initially diagnosed as having Bell's palsy. The third patient had negative serology at first assessment, on the basis of which the diagnosis of Lyme disease was temporarily rejected. Ultimately, all three appeared to have neuroborreliosis. They were treated with intravenous ceftriaxone and recovered well. Facial palsy in childhood is frequently caused by Lyme borreliosis and infection with Borrelia burgdorferi should therefore be investigated, even if there are no signs of a tick bite or erythema migrans. Diagnosis is made by serology, followed by immunoblotting to confirm a positive result. In case of strong suspicion based on the patient's history or physical examination or a positive serology, lumbar puncture should be carried out. Antibiotic treatment facilitates recovery and prevents complications.

Efficacy, safety and tolerability of 3 day azithromycin versus 10 day co-amoxiclav in the treatment of children with acute lower respiratory tract infections.

To compare the efficacy, safety and tolerability of a 3 day course of azithromycin with a 10 day course of co-amoxiclav in the treatment of children with acute lower respiratory tract infection (LRTI), 118 patients with community-acquired LRTI were included in a multicentre randomized double-blind, double-dummy study. The diagnosis of LRTI was based on the presence of respiratory signs and symptoms in combination with consolidation on a chest radiograph or clinical evidence of LRTI. Patients received oral azithromycin suspension (10 mg/kg/24 h) or placebo in one dose for 3 days and co-amoxiclav (45/11.25 mg/kg/24 h) or placebo in three doses for 10 days. Of 110 eligible patients, 56 and 54 patients, respectively, were treated with azithromycin or co-amoxiclav. The percentage of patients cured or clinically improved at days 10-13 (primary endpoint) was 91% for azithromycin and 87% for co-amoxiclav. This difference of 4% (90% confidence interval: -6%, +14%) was not statistically significant (P= 0.55). Significantly (P = 0.01) more related adverse events were found in the co-amoxiclav group. This was largely due to a higher percentage (43% versus 19%) of gastrointestinal complaints. A 3 day course of azithromycin (three doses) is as effective in the treatment of LRTI in children as a 10 day course of co-amoxiclav (30 doses). The azithromycin group had fewer adverse events. We conclude that azithromycin is an effective, safe and well-tolerated drug in the treatment of children with LRTI. An additional advantage is the easy administration and short duration of therapy.

Hospital admissions and readmissions for asthma in the age group 0-4 years.

SUMMARY. Childhood rates for admission and readmission for asthma are highest under the age of 5 years. From a registration study in 0-4-year-olds, 100 patients (68 male) were admitted to hospital for asthma and followed for 1 year, yielding a total of 136 admissions. To examine factors that may play a role in admissions and readmissions, histories and laboratory tests for atopic status at initial presentation, and clinical data on admission were evaluated. Age groups 0-1 year (n = 54) and 2-4 years (n = 46) were analyzed separately, of whom 20 (37%) and 9 (20%) patients, respectively, had at least one readmission. In the age group 2-4 years, patients with antibodies against inhalant allergens, determined by radioallergosorbent test (RAST), had a significantly higher risk of readmission (RR = 1.54; 95% CI, 1.22-1.95). In the age group 0-1, year prevalence of sensitization to inhalant allergens was low (20% vs. 72% in age group 2-4 years) and constituted only a slight risk (P = 0.097) for readmission. A history of eczema showed a negative association in the age group 0-1 year. Treatment of the first admission did not differ between children only admitted once and those requiring readmission. In both age groups, clinical features at admission did not differ significantly between first and subsequent admissions, and neither did length of stay. Number of readmissions were higher in the age group 0-1 year than in the age group 2-4 years (27/81 (33%) vs. 9/55 (16%), P = 0.028), with no indication of a lower threshold for admission. In the age group 0-1 year, 60% of the readmissions occurred within 2 months of first hospitalization. Moreover, in the age group 0-1 year a trend was observed that inhaled steroids were prescribed less frequently on discharge following first admission in those children who were readmitted than in the children who had a first admission only (4/20 (20%) vs. 15/34 (44%), P = 0.073). More "aggressive" therapy with anti-inflammatory drugs and close medical follow-up after discharge seem to be indicated.

Nasal peak inspiratory flow through Turbuhaler in children with symptomatic rhinitis and in healthy children.

Topical treatment of allergic or vasomotor rhinitis is possible by means of pressurized metered dose inhalers, aqueous spray, or dry powder inhalers. In children, little is known about nasal drug delivery by dry powder inhalation. The airflow through the device is critical for the drug release and a sufficient nasal inspiratory flow is needed for intranasal drug delivery from a dry powder inhaler. In order to investigate from what age children with allergic or vasomotor rhinitis can reliably use such a device, device-dependent nasal peak inspiratory flow (DnPIF) was measured. The maximal DnPIF was measured in children aged 4-13 years making use of a dry powder inhaler (Turbuhaler) connected to a spirometer (Vitalograph). In the clinically relevant context, instructions from the doctor and one week's use of a Turbuhaler at home were found to be sufficient to obtain a good inhalation technique and were shown to improve DnPIF at least as effectively as visual feedback training at the clinic. Children with rhinitis, as well as healthy children from the age of 6 years, were able to generate a DnPIF sufficient to obtain a reliable nasal delivery of a dry powder drug dose. DnPIF values correlated with age. Consequently, a recommendation to use a nasal Turbuhaler from the age of 6 for topical drug delivery in the treatment of allergic or vasomotor rhinitis seems reasonable.

Dose-responses over time to inhaled fluticasone propionate treatment of exercise- and methacholine-induced bronchoconstriction in children with asthma.

When treating bronchial hyperresponsiveness to so-called direct and indirect stimuli, distinct pathophysiological mechanisms might require differences in dose and duration of inhaled corticosteroid therapy. To test this hypothesis in children with asthma, we investigated the time- and dose-dependent effects of 2 doses of fluticasone propionate (FP, 100 or 250 microg bid.) in improving exercise- (EIB) and methacholine-induced bronchoconstriction during 6 months of treatment, using a placebo-controlled parallel group study design. Thirty-seven children with asthma (aged 6 to 14 years; forced expired volume in 1 sec (FEV(1)) >/=70% predicted; EIB >/=20% fall in FEV(1) from baseline; no inhaled steroids during the past 4 months) participated in a double-blind, placebo-controlled, 3-arm parallel study. Children receiving placebo were re-randomized to active treatment after 6 weeks. Standardized dry air treadmill exercise testing (EIB expressed as %fall in FEV(1) from baseline) and methacholine challenge using a dosimetric technique (expressed as PD(20)) were performed repeatedly during the study. During FP-treatment, the severity of EIB decreased significantly as compared to placebo within 3 weeks, the geometric mean % fall in FEV(1) being reduced from 34.1% to 9.9% for 100 microg FP bid, and from 35.9% to 7.6% for 250 microg FP bid (P < 0.05). These reductions in EIB did not differ between the 2 doses and were sustained throughout the treatment period. PD(20) methacholine improved significantly during the first 6 weeks as compared to placebo (P < 0.04) and steadily increased with time in both treatment limbs (P = 0.04), the difference in improvement between doses (100 microg FP bid, 1.6 dose steps; 250 microg FP bid, 3.3 dose steps) approaching significance after 24 weeks (P = 0.06). We conclude that in childhood asthma, the protection afforded by inhaled fluticasone propionate against methacholine-induced bronchoconstriction is time- and dose-dependent, whereas protection against EIB is not. This suggests different modes of action of inhaled steroids in protecting against these pharmacological and physiological stimuli. This has to be taken into account when monitoring asthma treatment.

Risk factors for exacerbations and hospital admissions in asthma of early childhood.

Hospital admissions and readmissions for asthma in early childhood remain causes for concern. The purpose of this study was to identify predisposing risk factors related to asthma exacerbations and precursors of hospital admissions in young children. Subjects were patients with doctor-diagnosed asthma from a clinical registration study, aged 0-4 years, and followed up for 2 years. Data from histories and laboratory tests for atopic status at initial presentation, and the patient's condition at visits over the 2-year follow-up period were evaluated. Exacerbation was defined as increases in cough and/or wheeze and/or breathlessness, increase in beta(2)-agonist use, and a clinical need for a short course of oral corticosteroids. Age groups 0-1 year and 2-4 years, based on age at initial presentation, were analyzed separately. In the age group 0-1 year, 71/113 (63%) patients had at least one exacerbation, and 20 experienced recurrent exacerbations (>/=3). Predisposing risk factors for exacerbation were damp housing (odds ratio (OR) 7.6 (2. 0-28.6)) and colds (OR 3.6 (1.4-9.6)), and for recurrent exacerbations sensitization to inhalant allergens (Phadiatop(R)) (OR 8.1 (1.6-40.5)) and damp housing (OR 3.8 (1.1-12.8)). Hospital admissions were significantly associated with number of exacerbations. In the age group 2-4 years, 58/144 (40%) patients had at least one exacerbation, and 21 experienced recurrent exacerbations (>/=2). Predisposing risk factors for exacerbation were mean age at initial presentation (OR 0.92 (0.88-0.97)) and level of total IgE (OR 2.3 (1.4-3.9)), whereas for recurrent exacerbations no predictor variables were found. Hospital admissions were significantly associated with damp housing. Results from this study may facilitate recognition of young asthmatic patients at risk of (recurrent) exacerbations, and help to identify those in whom early intervention with anti-inflammatory therapy may be necessary. We also emphasize the importance of preventive measures in decreasing damp housing.

Prognostic characteristics of asthma diagnosis in early childhood in clinical practice.

A registration study from clinical practice was set up to assess the prognostic value of symptoms and laboratory data at first visit for doctor-diagnosed 'asthma' in early childhood. A total of 419 children aged 0-4 y, who were newly referred to the outpatient department of the Juliana Children's Hospital with possible asthma were enrolled over a 2-y period. Data from history taking, physical examination, laboratory tests for atopic status at first visit and data from follow-up visits were recorded. Two years after the first visit all medical records were reviewed for diagnostic label. The age groups 0-1 y and 2-4 y were analysed separately, because respiratory symptoms are often transient and sensitization to inhalant allergens is uncommon before the age of 2 y. The clinical diagnosis 'asthma' was made in 113 of 231 (49%) children aged 0-1 y and in 144 of 188 (77%) children aged 24 y. Characteristics from history taking indicated shortness of breath was the most prognostic symptom in both age groups. Eczema, wheeze and non-allergic provoking factors (weather conditions) were further predisposing factors in the 0-1 y group, as were allergic provoking factors (inhalant allergens) and absence of ear-nose-throat-history in the 2-4 y group. Adding laboratory data to history total serum IgE had prognostic value, but specific serum IgE against inhalant allergens (Phadiatop) was a strong predisposing factor, especially in the 2-4 y group. These prognostic characteristics may enhance early recognition of asthma in infants and improve asthma care in clinical practice.

[Acute respiratory insufficiency in children]. / Acute respiratoire benauwdheid bij kinderen.

Acute respiratory distress in children is often a consequence of asthma. Other causes are subglottic laryngitis, epiglottitis, aspiration of a foreign body, acute bacterial pneumonia or pneumothorax. History and physical examination should differentiate between the various diseases. Asthma is characterized by recurrent symptoms and signs, while this is not the case with the other causes of acute breathlessness described. An asthma exacerbation is often preceded by one or more prodromes. In case of aspiration of a foreign body, like a peanut, immediate action is needed to prevent irreversible damage to the airways. Subglottic laryngitis and epiglottitis are both characterized by an inspiratory stridor; in case of epiglottitis immediate action is needed, while in case of subglottic laryngitis observation time is available in most cases. Pneumothorax as a cause of acute breathlessness is rare in childhood; it should be considered in male smoking leptosomic asthmatic adolescents.

Occurrence of a late response to exercise in asthmatic children: multiple regression approach using time-matched baseline and histamine control days.

At the present time, there is still controversy concerning the presence of a late asthmatic response (LAR) to exercise challenge in asthma. We have, therefore, investigated the occurrence of a LAR after exercise in asthmatic children visiting an out-patient clinic, using time-matched baseline and histamine control days, and a statistical analysis according to recently published recommendations. After a screening exercise day, 17 children (aged 7-14 yrs) randomly performed, on three subsequent study days, either: a second standardized exercise challenge; or a histamine challenge whilst matching the bronchoconstriction after exercise; or measurement of baseline lung function without any challenge. Measurements of forced expiratory volume in one second (FEV1) were made repeatedly during 8 h. Analysis was performed using multiple regression analysis for each patient, with FEV1 as the dependent, and test day (exercise or control) and clock time as independent variables during the period 2-8 h after exercise. A significant interaction (p < 0.05) between test day and clock time was considered to be indicative of a LAR. Fifteen children completed the study. All children showed an early asthmatic reaction to exercise (range 14-62% fall in FEV1). In two children, a significant interaction (p < 0.05) was found between test day and clock time. However, the difference in FEV1 between exercise and control days for each clock time did not exceed the 99.6% confidence limits of normal diurnal variation in any of the children. We conclude that, in children with mild-to-moderate asthma, a LAR to exercise does not occur. This suggests that exercise is only a symptomatic trigger of asthma. Whether exercise is capable of inducing inflammation needs to be further investigated.

Prolonged recovery from exercise-induced asthma with increasing age in childhood.

It has been suggested that children with asthma recover more quickly from exercise-induced bronchoconstriction than adults. On the basis of clinical observation we hypothesized that recovery rate from exercise-induced asthma (EIA) in childhood also decreases with age. In 14 children (aged 7-12 years) with a history of EIA, we measured spontaneous recovery from bronchoconstriction induced by two different stimuli: exercise and histamine. The children visited the laboratory three times. After a screening exercise test on the first visit, standardized bronchoprovocation tests with either exercise or histamine were performed on the following two visits in random order. The degree of bronchoconstriction induced by histamine was matched for that observed after exercise. During recovery, forced expiratory volume in 1 second (FEV1) was measured repeatedly up to 2 hours postchallenge. The recovery rate (% increase in FEV1/min) was calculated from the linear slope of the time-response curve. Differences in recovery rate between the two stimuli were analyzed by paired t-test, and age-related differences were analyzed using multiple regression analysis. For the group as a whole, recovery rate was not different between the two stimuli (mean +/- SD: 1.22 +/- 0.91 for exercise, and 1.46 +/- 0.65, for histamine, P = 0.31). However, the recovery rate for exercise-induced bronchoconstriction decreased significantly with age (r = -0.74, P = 0.003), in contrast to the recovery rate for histamine (r = -0.15, P = 0.60). Consequently, in the oldest age group (11-12 years, n = 5) recovery rate from exercise challenge was significantly slower than in the younger age group (7-10 years, n = 9), i.e., 0.54 +/- 0.17 and 1.60 +/- 0.93, respectively, P = 0.009, and slower than the recovery rate from histamine challenge: 0.54 +/- 0.17 and 1.33 +/- 0.54, respectively, P = 0.03. In the younger age group the recovery rates from exercise and histamine were not different (1.60 +/- 0.93 and 1.54 +/- 0.73, respectively, P = 0.83). We conclude that recovery from EIA in childhood decreases with increasing age. These data suggest that the mechanism of exercise-induced asthma in childhood changes with age. This might be due to changes in mediator production or response to mediator release.

Large lungs after childhood asthma. A case-control study.

Several studies have suggested that the TLC after childhood asthma is increased compared wtih that in healthy subjects. The aim of this study was to assess whether TLC is increased after childhood asthma and whether this is associated with an increased growth of the lung during adolescence. During a mean period of 29 months we studied 53 patients and 106 healthy control subjects who were matched for sex, age, and standing height. The patients had had asthma for a mean period of 10 yr. We found that in asthmatics TLC was increased in both sexes by about 7% predicted compared with that in the matched control subjects. The growth of TLC in ml/yr during adolescence was less in patients; this can be accounted for by a delay in pubertal development. When corrected for the delay in growth of stature, growth of TLC in ml/cm in asthmatics was similar to that found in control subjects. These findings support the hypothesis of a developmental change of enhanced lung growth during childhood asthma; they do not support a mechanism with progressive loss of elastic recoil of the lung.