High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.

BACKGROUND: The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. OBJECTIVE: To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. METHODS: Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. RESULTS: A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). CONCLUSION AND CLINICAL RELEVANCE: Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.

Lower anti-echovirus antibody responses in children presenting to hospital with asthma exacerbations.

BACKGROUND: Rhinoviruses from the Enterovirus genus cause frequent infections and induce remarkably high titres of anticapsid antigen antibodies in asthmatics, while the prevalence of neutralising antibodies to the gut-trophic echoviruses from the same genus is diminished. OBJECTIVE: To assess the absolute and specific antibody titres to VP1 antigens of the gut-trophic enteroviruses, echovirus 30 and Sabin 1 poliovirus, in asthmatic and non-asthmatic children. METHODS: Recombinant polypeptides representing the VP1 capsid antigens of echovirus 30 and Sabin poliovirus 1 were produced. Their ability to bind IgG1 antibodies from the plasma of asthmatic (n = 45) and non-asthmatic (n = 29) children were quantitated by immunoassays that incorporated immunoabsorptions to remove cross-reactivity. RESULTS: The IgG1 antibody titres and prevalence of antibody binding to echovirus 30 were significantly lower for asthmatic children compared to controls (P < 0.05) and inversely correlated with total IgE levels for the whole study population (r = -0.262; P < 0.05). There was no difference in the prevalence and titre between groups to the VP1 antigen of Sabin poliovirus. Anti-tetanus toxoid titres measured for comparison did not correlate with anti-echovirus or poliovirus, but correlated with anti-rhinovirus titres in controls but not asthmatics, where the titres were higher for the asthmatic group. CONCLUSIONS AND CLINICAL RELEVANCE: The associations of lower antibody titres of asthmatic children to echovirus reported here and those of our previous findings of a heightened response to rhinovirus suggest a dichotomy where respiratory enterovirus infection/immunity increases the probability of developing asthma and enteric infections lower the risk. This provides further support for the concept of intestinal infection playing a key role in the development of allergic respiratory disease.

Rhinovirus and the developing lung.

Human rhinovirus (HRV) infections are now widely accepted as the commonest cause of acute respiratory illnesses (ARIs) in children. Advanced PCR techniques have enabled HRV infections to be identified as causative agents in most common ARIs in childhood including bronchiolitis, acute asthma, pneumonia and croup. However, the long-term implications of rhinovirus infections are less clear. The aim of this review is to examine the relationship between rhinovirus infections and disorders of the lower airways in childhood.

EAACI position statement on asthma exacerbations and severe asthma.

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

Association between human rhinovirus C and severity of acute asthma in children.

A new and potentially more pathogenic group of human rhinovirus (HRV), group C (HRVC), has recently been discovered. We hypothesised that HRVC would be present in children with acute asthma and cause more severe attacks than other viruses or HRV groups. Children with acute asthma (n = 128; age 2-16 yrs) were recruited on presentation to an emergency department. Asthma exacerbation severity was assessed, and respiratory viruses and HRV strains were identified in a nasal aspirate. The majority of the children studied had moderate-to-severe asthma (85.2%) and 98.9% were admitted to hospital. HRV was detected in 87.5% and other respiratory viruses in 14.8% of children, most of whom also had HRV. HRVC was present in the majority of children with acute asthma (59.4%) and associated with more severe asthma. Children with HRVC (n = 76) had higher asthma severity scores than children whose HRV infection was HRVA or HRVB only (n = 34; p = 0.018), and all other children (n = 50; p = 0.016). Of the 19 children with a non-HRV virus, 13 had HRV co-infections, seven of these being HRVC. HRVC accounts for the majority of asthma attacks in children presenting to hospital and causes more severe attacks than previously known HRV groups and other viruses.

The importance of environment on respiratory genotype/phenotype relationships in the Inuit.

BACKGROUND: Genetic and environmental influences and their interactions are central to asthma pathogenesis. This study aimed to investigate the effects of different macro-environments on asthma genotype-phenotype associations in two geographically separated populations with common ancestry. METHODS: To accomplish this, two unselected populations of Inuit were recruited, one living in Greenland (n = 618) and the other in Denmark (n = 739). Subjects were genotyped for CD14 C-159T, SCGB1A1 A38G, ADRB2 Arg16Gly and Gln27Glu. The resulting genetic data were analysed for relationships with asthma-related parameters including lung function, ever asthma, atopy, rhinitis and dermatitis. RESULTS: The results showed contrasting magnitude and direction of genetic associations between the two geographically separate Inuit populations. In Greenland, the ADRB2 16Arg allele was associated with male-specific lower lung function, but in Denmark the same allele was associated with male-specific higher lung function. This allele was also associated with higher incidence of ever asthma in Denmark but not in Greenland. The SCGB1A1 38A allele was associated with lower rhinitis prevalence in Greenland but not in Denmark. CONCLUSIONS: These associations suggest that environment interacts with candidate asthma genes to modulate asthma pathogenesis in the Inuit.

The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze.

BACKGROUND: A recently proposed method for classifying preschool wheeze is to describe it as either episodic (viral) wheeze or multiple trigger wheeze. In research studies, phenotype is generally determined by retrospective questionnaire. AIM: To determine whether recently proposed phenotypes of preschool wheeze are stable over time. METHODS: In all, 132 two to six-year-old children with doctor diagnosed asthma on maintenance inhaled corticosteroids were classified as having episodic (viral) wheeze or multiple trigger wheeze at a screening visit and then followed up at three-monthly intervals for a year. At each follow-up visit, standardized questionnaires were used to determine whether the subjects wheezed only with, or also in the absence of colds. Stability of the phenotypes was assessed at the end of the study. RESULTS: Phenotype as determined by retrospective parental report at the start of the study was not predictive of phenotype during the study year. Phenotypic classification remained the same in 45.9% of children and altered in 54.1% of children. CONCLUSION: When children with preschool wheeze are classified into episodic (viral) wheeze or multiple trigger wheeze based on retrospective questionnaire, the classification is likely to change significantly within a 1-year period.

Investigations into the role of ST2 in acute asthma in children.

The ST2 gene is a member of the interleukin-1 receptor family and is located on chromosome 2q12, an area of the genome that has been associated with asthma. The soluble product of the ST2 gene, serum ST2 (sST2), has previously been shown to be elevated in adult asthmatic patients. This study investigated the potential role of ST2 in children with acute asthma. Children aged 2-16 years (n = 186) were recruited on presentation with acute asthma in the emergency department. Blood was obtained on presentation and during convalescence. Variables assessed included sST2 levels, a comprehensive assembly of clinical parameters and two polymorphisms in the ST2 gene, -26999G/A, located in the distal promoter region, and ala78glu polymorphism, on exon 3. The A allele of the -26999G/A polymorphism occurred more frequently in asthmatics compared with an unselected control group (P = 0.031). Serum ST2 levels were substantially higher during acute asthma compared with levels after the attack: 0.29 ng/ml (95% confidence interval: 0.23-0.36) and 0.14 ng/ml (0.12-0.17), respectively (P = 0.001) and were inversely related to eosinophil counts during an acute asthma attack (P = 0.002). The -26999AA genotype, as well as the AC haplotype, was associated with asthma severity scores (P = 0.05 and 0.02) compared with the -26999GA and GG genotypes. Serum ST2 levels were not associated with any of the studied genotypes or haplotypes. The observed associations of ST2 genotypes and haplotypes with acute asthma and asthma severity scores as well as the phenotypic differences associated with ST2 polymorphisms suggest that ST2 may play a role in the pathophysiology of asthma.

Cross-sectional and longitudinal association of the secretoglobin 1A1 gene A38G polymorphism with asthma phenotype in the Perth Infant Asthma Follow-up cohort.

BACKGROUND: Associations between Clara cell secretory protein gene variants (SCGB1A1, also known as CC16, CC10, CCSP and uteroglobin) and the asthma phenotype have been found in five out of eight studies world-wide. No study has investigated the contribution of SCGB1A1 polymorphisms to the development and/or persistence of the asthma phenotype in a birth cohort followed over time. OBJECTIVE: The aim of this study was to determine the role of the SCGB1A1 gene in the development of the asthma phenotype. METHODS: The Perth Infant Asthma Follow-up (PIAF) cohort (n=231 unrelated infants, unselected for asthma and recruited at birth) were seen at 1 month, 6 and 11 years of age, and had a questionnaire, lung function, airway responsiveness (AR) and skin prick tests (SPTs) completed. Blood was taken at 6 and 11 years for total and specific immunoglobulin E (sIgE) and DNA extraction. SPT positivity had at least one positive SPT. SIgE>4 kU/L had at least one sIgE above 4 kU/L. SCGB1A1 A38G (rs3741240), that alters gene transcription, was genotyped using Sau96I restriction digestion of exon 1 PCR products. RESULTS: At 6 and 11 years of age, 33.0% and 29.7% of those genotyped had doctor-diagnosed asthma, and 35.8% and 52.1% had SPT positivity. In cross-sectional analyses, children with 38G/38A or 38A/38A had increased AR at 1 month (1.72-fold, P=0.013); sIgE>4 kU/L [odds ratio (OR)=6.95, 95% confidence interval (CI)=1.35-35.91, P=0.021]; house dust mite (HDM) SPT positivity (OR=7.21, 95% CI=1.09-47.78, P=0.041) and sIgE (4.57-fold, P=0.045) at 6 years; and doctor-diagnosed asthma (OR=3.93, 95% CI=1.24-12.47, P=0.02) and cat SPT positivity (OR=4.34, 95% CI=1.01-18.77, P=0.049) at 11 years. Longitudinal analyses of 6 and 11 years paired data showed that children with 38A/38A had increased persistent sIgE>4 kU/L (OR=11.87, 95% CI=1.97-71.53, P=0.007) and persistent HDM SPT positivity (OR=7.84, 95% CI=1.04-58.92, P=0.045). CONCLUSION: SCGB1A1 A38G may play a role in the development and persistence of the asthma phenotype in childhood.

Opposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergy.

BACKGROUND: Finnish Karelians have a higher prevalence of allergic disease than Russian Karelians. As both populations are generally from the same ethnic group, the Karelian population offers a unique opportunity to analyse genetic and allergic disease interactions between 'Western' and 'Eastern' environments. OBJECTIVES: We investigated associations between allergic diseases and CD14 and CC16 polymorphisms in Finnish vs Russian Karelian women. METHODS: Adult female Karelians (330 Finnish and 274 Russian) were recruited, examined for a range of symptoms and conditions including rhinitis, itchy rash, asthma and atopy and genotyped for CD14 C-159T and CC16 A38G. RESULTS: For both CD14 C-159T and CC16 A38G, the risk allele for atopic phenotypes in Finnish Karelia was the protective allele in Russian Karelia. For CD14 C-159T, an interactive effect on ever itchy rash (P(interaction) = 0.004), itchy rash <12 mo (P(interaction) = 0.001) and dry cough at night in the past 12 months (<12 months) (P(interaction) = 0.011) was found; the risk allele was C in Russians and T in Finns. For CC16 A38G, an interaction was significant for ever rhinitis (P(interaction) = 0.006), rhinitis <12 mo (P(interaction) = 0.004), and marginally significant for ever hayfever (P(interaction) = 0.07), allergic eye symptoms <12 mo (P(interaction) = 0.09); their risk allele was G in Russians and A in Finns. CONCLUSION: An Eastern vs Western environment appears to exert an effect via opposite alleles on risk of allergic diseases in adult women.

Associations between postnatal weight gain, change in postnatal pulmonary function, formula feeding and early asthma.

BACKGROUND: A study was undertaken to examine factors that might influence lung function during infancy and to test the hypothesis that change in weight during infancy is negatively associated with change in lung function. METHODS: Weight, length and maximal flow at functional residual capacity (V'maxFRC) were measured at ages 1 and 12 months. V'maxFRC was adjusted for length. Asthma symptoms and age at introduction of formula feeds were identified from questionnaires. Groups were dichotomised by V'maxFRC at 1 month and change in V'maxFRC. RESULTS: 154 infants were assessed at ages 1 and 12 months. The change in V'maxFRC was inversely associated with change in weight (r = -0.18, r2 = 0.13, p<0.001). The group with lower V'maxFRC at 1 month and reduced change in V'maxFRC over infancy had the greatest weight gain (p = 0.003) and increased risk for asthma symptoms by 3 years (p = 0.017) but not afterwards. Exclusive breast feeding to 6 months was associated with a mean reduction in weight gain at age 12 months in comparison with earlier introduction of formula milk (mean difference 0.65 kg, p = 0.001), and was also associated with reduced asthma symptoms at 3 years (odds ratio 0.44, p = 0.043) but not at 6 or 11 years of age. CONCLUSIONS: Weight gain in infancy is inversely associated with change in lung function during infancy. Postnatal weight gain may be indirectly associated with early transient asthma symptoms via an influence on lung growth during infancy, and this is potentially modifiable by breast feeding. These associations could be relevant to the clinically recognised syndrome of the "fat happy wheezer".

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach.

There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes.

Total IgE in urban Black South African teenagers: the influence of atopy and helminth infection.

Total IgE levels are usually elevated in allergic diseases, being highest in atopic eczema, followed by atopic asthma and allergic rhinitis. Genetic factors are believed to play a role in total IgE levels, with higher levels seen in Black African subjects. Total IgE is also raised in parasite infection. Thus, the higher total IgE levels in Black Africans could be because of environmental rather than genetic factors. Few studies have investigated the usefulness of total IgE levels in the evaluation of atopy in Black Africans. The objective of this study was to determine the total IgE levels in unselected urban Black African high school children and to correlate this with atopy and ascaris sensitization. Atopic status was assessed by means of specific allergen sensitization (skin prick tests to eight inhalant and four food allergens), self-reported asthma and bronchial hyper-responsiveness measured by methacholine challenge. Ascaris sensitization was assessed by means of ascaris IgE measured by CAP-RAST. Total IgE levels were markedly skewed toward the left and were not distributed in a Gaussian or a log-normal distribution. Skin prick tests were positive for aeroallergens in 32.3% of subjects. Thirty four percent had elevated ascaris IgE. Total IgE was higher in atopic vs. non-atopic subjects and correlated with the number of positive skin prick tests, self-reported asthma and bronchial hyper-responsiveness. Subjects without allergy (or) atopy had a median total IgE of 80-90 kU/I. In addition total IgE correlated with ascaris IgE. Subjects with no ascaris sensitization had median total IgE of 77.1 kU/l. Subjects with neither atopy/asthma nor ascaris sensitisation had a median total IgE of 69.9 kU/I, similar to the levels seen in people of other genetic origins. This study suggests that helminthic infection rather than genetic differences, may be the major determining factor of IgE levels in certain populations.

An immunoepidemiological approach to asthma: identification of in-vitro T-cell response patterns associated with different wheezing phenotypes in children.

BACKGROUND: Increasing evidence suggests that patterns of T-cell immunity to inhalant allergens in genetically diverse human populations are more heterogeneous than previously assumed, and that covert differences in expression patterns might underlie variations in airway disease phenotypes. We tested this proposition in a community sample of children. METHODS: We analysed data from 172 individuals who had been recruited antenatally to a longitudinal birth cohort study. Of the 194 birth cohort participants, data from the 147 probands (age range 8.6-13.5 years) who consented to blood collection were included along with data from 25 consenting siblings (mean age 11 years [range 7.4-17.4]). We ascertained clinical phenotypes related to asthma and allergy. We measured T-cell responses to allergens and mitogens, together with blood eosinophils and IgE/IgG antibodies, and assessed associations between these indices and clinical phenotypes. FINDINGS: Atopy was associated with allergen-specific T-helper (Th)2 responses dominated by interleukin 4, interleukin 5, interleukin 9, interleukin 13, whereas interleukin 10, tumour necrosis factor alpha, and interferon gamma responses were common to both atopics and non-atopics. The wheal size from skin prick with allergen was positively associated with in-vitro interleukin 5 and interferon gamma responses, and negatively associated with interleukin 10. Asthma, especially in atopics, was strongly associated with eosinophilia/interleukin 5, and bronchial hyper-responsiveness (BHR) was associated with eosinophilia plus polyclonal interferon gamma production. BHR in non-atopics was associated with elevated allergen-specific and polyclonal interleukin 10 production. INTERPRETATION: Parallel immunological and clinical profiling of children identified distinctive immune response patterns related to asthma and wheeze compared with BHR, in atopics non-atopics. Immunological hyper-responsiveness, including within the Th1 cytokine compartment, is identified as a hallmark of BHR. RELEVANCE TO PRACTICE: These findings highlight the heterogeneity of immune response patterns in asthmatic children, including those with seemingly homogeneous Th2-driven atopic asthma. Further elucidation of the covert relationships between wheezing phenotypes and underlying immunophenotypes in this age group will potentially lead to more effective treatments for what is an unexpectedly heterogeneous collection of disease subtypes.

Association of haplotypes of beta2-adrenoceptor polymorphisms with lung function and airway responsiveness in a pediatric cohort.

We evaluated the influence of haplotypes of beta(2)-adrenergic receptor (ADRB2) polymorphisms on lung function and airway responsiveness (AR) in a pediatric cohort recruited before birth and followed up to 11 years of age. The subjects (180) were the participants in a prospective study of lung function and AR. They have been assessed five times (at 1 month, 6 months, 12 months, 6 and 11 years of age) for lung function and AR. The two ADRB2 single nucleotide polymorphisms (SNPs): Arg16Gly and Gln27Glu were genotyped by PCR-RLFP and their haplotypes inferred using the program PHASE. An association between the haplotype arg16gln27 and the prevalence of positive AR was found at age 6 years (P = 0.009). The gly16gln27 haplotype was associated with higher FEV1 (P = 0.015) at age 6 and both higher FEV1 and FVC (P = 0.018 and P = 0.001, respectively) at age 11. In contrast, arg16gln27 was associated with both lower FEV1 and FVC (P = 0.028 and P = 0.011, respectively) at age 11. Children with the gly16gln27 haplotype were less likely to have asthma-ever or doctor-diagnosed asthma at age 11 (OR: 0.38; P = 0.019 and OR: 0.31; P = 0.041, respectively). In conclusion, haplotypes of beta(2)-adrenoceptor polymorphisms are associated with lung function, AR, and asthma susceptibility in childhood.

Comparison of transcutaneous oxygen tension with arterial oxygen tension in newborn infants with severe respiratory illnesses.

Transcutaneous oxygen tension (tcPO2), measured by two skin electrodes of different design, and arterial oxygen tension (PaO2), measured by an intravascular oxygen electrode, were continuously recorded for periods of six hours in 15 newborn infants with serious respiratory illnesses. Ten of the infants needed mechanical ventilation and three needed continuous positive airway pressure. One skin electrode had three microcathodes surrounded by a heated ring-shaped anode, and the other had a large heated cathode. The temperature of both electrodes was set at 44 degrees C and they were calibrated in vitro. The tcPO2 recorded by the electrode with the microcathodes was found to estimate PaO2 reasonably accurately for the whole six-hour duration of the study. The tcPO2 recorded by the electrode with the large cathode gave a similar estimate of PaO2 for three hours, but then tcPO2 often fell relative to PaO2. This fall was probably caused by skin changes at the electrode site. For a variety of reasons, our results suggest that measurement of tcPO2 is unlikely to replace continuous intravascular measurement of PaO2 in infants with severe respiratory illnesses.

Growth and development of the lung.

Over the last half of the last century, classic studies established many features of the development of the lung in humans. Early studies relied on meticulous measurement and evaluation of lung morphology and physiology. In recent years, such studies have been supplemented by carefully conducted, longitudinal studies and by the use of molecular biological methodologies to determine more detailed aspects of lung development. In addition, factors affecting the growth of the lung have been evaluated including preterm delivery, antenatal steroids, environmental factors, asthma and asthma medications. In the future, further advances are likely to come from the molecular biological approach.

Effect of compression pressure on forced expiratory flow in infants.

The effect of the force of compression on expiratory flow was evaluated in 19 infants (2-13 mo of age) with respiratory illnesses of varying severity. An inflatable cuff was used to compress the chest and abdomen. Expiratory flow and volume, airway occlusion pressure, cuff pressure (Pc), and functional residual capacity were measured. Transmission of pressure from cuff to pleural space was assessed by a noninvasive occlusion technique. Close correlations (P less than 0.001) were found between Pc and the change in pleural pressure with cuff inflation (delta Ppl,c). Pressure transmission was found to vary between two cuffs of different design and between infants. Several forced expirations were then performed on each infant at various levels of delta Ppl,c. Infants with low maximal expiratory flows at low lung volumes required relatively gentle compression to achieve flow limitation and showed decreased flow for firmer compressions. Flow-volume curves in each infant tended to become more concave as delta Ppl,c increased. These findings underline the importance of knowledge of delta Ppl,c in interpreting expiratory flow-volume curves in infants.