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Paul T King,1,2 Stephen R Holdsworth,2 Michael Farmer,1 Nicholas J Freezer,1 Peter W Holmes11Department of Respiratory and Sleep Medicine, 2Monash University Department of Medicine, Monash Medical Centre, Melbourne, Victoria, AustraliaBackground: Bronchiectasis is a common disease and a major cause of respiratory morbidity. Chest pain has been described as occurring in the context of bronchiectasis but has not been well characterized. This study was performed to describe the characteristics of chest pain in adult bronchiectasis and to define the relationship of this pain to exacerbations.Subjects and methods: We performed a prospective study of 178 patients who were followed-up for 8 years. Subjects were reviewed on a yearly basis and assessed for the presence of chest pain. Subjects who had chest pain at the time of clinical review by the investigators were included in this study. Forty-four patients (25%) described respiratory chest pain at the time of assessment; in the majority of cases 39/44 (89%), this occurred with an exacerbation and two distinct types of chest pain could be described: pleuritic (n = 4) and non-pleuritic (n = 37), with two subjects describing both forms. The non-pleuritic chest pain occurred most commonly over both lower lobes and was mild to moderate in severity. The pain subsided as patients recovered. Conclusion: Non-pleuritic chest pain occurs in subjects with bronchiectasis generally in association with exacerbations.Keywords: sputum, collapse, bronchitis, airway obstruction

BACKGROUND: Recent studies described a progressive decline in lung volumes in adult bronchiectasis. Interstitial lung disease is also a feature of bronchiectasis, but whether this is associated with a decline in lung diffusing capacity (measured as the diffusing capacity of the lung for carbon monoxide [DLCO]) is not well known. OBJECTIVE: To assess longitudinal decline in diffusing capacity of the lung for carbon monoxide (DLCO) in adult bronchiectasis. METHODS: Sixty-one subjects had a detailed baseline clinical and laboratory assessment, then were followed regularly with clinical and lung-function assessment for a median 7 years. RESULTS: Baseline spirometry demonstrated mild obstructive lung disease, with a mean FEV1 of 72% of predicted, mean forced vital capacity 87% of predicted, and normal DLCO (mean DLCO 88% of predicted, and mean DLCO adjusted for alveolar volume [DLCO/VA] 100% of predicted). There was an accelerated decline in DLCO and DLCO/VA over the 7-year period. The median DLCO decline was 2.9% of predicted per year (95% CI 2.3-4.1% of predicted per year). The median DLCO/VA decline was 2.4% of predicted per year (95% CI 2.1-4.0% of predicted per year). There was a significant relationship between DLCO decline and age and decline in FEV1. CONCLUSIONS: In our cohort of patients with bronchiectasis there was a progressive DLCO decline. [ABSTRACT FROM AUTHOR]

Objectives: To describe experience with subglottic haemangioma in a unit where conservative treatment has been favoured.Methods: Retrospective case note review of infants presenting with subglottic haemangioma over a 25 year period.Results: Thirty one infants were identified. Diagnosis was difficult where skin haemangiomas were absent and where the lesion was circumferential rather than asymmetrical. Tracheostomy was safe, well tolerated, and managed by the patients' family at home. Major complications were seen only when laser treatment was used.Conclusions: Aggressive treatment with substantial risks of long term complications may not be necessary in this spontaneously resolving disorder. [ABSTRACT FROM AUTHOR]

Individuals with asthma are prone to viral and bacterial infections, and most asthma exacerbations have been linked to viruses, particularly rhinovirus. Excess transforming growth factor (TGF)-beta present in asthmatic airways may cause immune suppression, as well as transdifferentiate fibroblasts to myofibroblasts, thereby augmenting proinflammatory responses after rhinovirus infection. After rhinovirus infection we examined virus replication and host cell immune responses in airway fibroblasts in the presence of TGF-beta1 and in myofibroblasts. Primary culture fibroblasts were pretreated with TGF-beta1 or transdifferentiated into myofibroblasts, and then infected with rhinovirus. Viral replication, virus release, chemokine production, and interferon (IFN) responses were measured over 72 hours. Rhinovirus replication and virus release into supernatants were enhanced in fibroblasts incubated with TGF-beta1 and in fibroblasts obtained from patients with asthma. Myofibroblasts also showed more rhinovirus replication, and infected myofibroblasts produced excess neutrophil chemokines. Examination of innate responses revealed blunting of type I IFN reactions with dissociated viral RNA and IFN mRNA responses. Addition of type I IFN restituted antiviral responses, and the effect of TGF-beta1 appeared to be mediated via actions on IFN regulatory factor-3 pathways. These data demonstrate that TGF-beta1 mediates enhanced virus replication and proinflammatory responses in airway cells. TGF-beta may act as an endogenous immunosuppressant promoting virus replication and inflammation during the evolution of acute severe asthma associated with rhinovirus infection.

Background and Objective: Stable asthma is characterized by the production of Th2 cytokines, although Th1 cytokines may play a key role in aspects such as airway hyper-responsiveness. This study explored cytokine profiles associated with asthma exacerbation., Methods: Intracellular T-cell cytokine production was measured in 16 children with acute severe asthma (emergency department), after convalescence (6 weeks, n = 13), with stable disease (after 6 months, n = 7) and in 14 age-matched hospital controls. Flow cytometry was used to identify CD4+ and CD8+ cells and to quantify intracellular T-cell production of the cytokines interferon (IFN)-gamma, IL-4 and IL-13. Cytokine production was compared using analysis of variance and random-effects generalized linear models and associations were examined using Pearson's correlation., Results: Cytokine production was evident in CD4+ and CD8+ cells, and compared with asthmatic children, non-asthmatics had a higher percentage of IFN-gamma+CD4+ cells (P = 0.01). The percentage of CD8+IFN-gamma+ cells was increased in the convalescent phase compared with acute (P = 0.009) and stable asthma (P = 0.004). IL-4+ cells were not significantly altered. IL-13 levels were higher in acute disease than in stable asthma (P = 0.009 in CD4+ cells) and IFN-gamma/IL-13 ratios indicated a Th2 profile during exacerbation (P = 0.005 in CD4+ cells)., Conclusions: IL-13, rather than IL-4, may play a pro-inflammatory role during acute severe asthma, whereas IFN-gamma responses were associated with recovery from acute severe asthma. These results suggest that altered T-cell cytokine profiles may contribute to the pathogenesis of and recovery from asthma exacerbations.

There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis. Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis. A prospective study of clinical and microbiologic outcomes was performed. Subjects were assessed by a respiratory physician and sputum sample were collected for analysis. Subjects were followed up and had repeat assessment performed. Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years. On initial assessment the two most common pathogens isolated were Haemophilus influenzae (47%) and Pseudomonas aeruginosa (12%) whilst 21% had no pathogens isolated. On follow-up review results were similar (40% H. influenzae, 18% P. aeruginosa and 26% no pathogens). The prevalence of antibiotic resistance of isolates increased from 13% to 30%. Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes. Subjects with no pathogens isolated from their sputum had the mildest disease, while subjects with P. aeruginosa had the most severe bronchiectasis. Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years. Different pathogens are associated with different patterns of clinical disease.

Background: There is little information available on the features of initial presentation of bronchiectasis and documentation of the onset and progress of symptoms leading up to this. Therefore a study was performed on a large cohort of adult patients presenting to Monash Medical Centre (MMC) to survey the course of their disease up to the time of diagnosis., Objectives: To characterise the onset and presenting clinical features of bronchiectasis in adults., Methods: A cross-sectional study of 103 adults presenting to a tertiary referral hospital with newly diagnosed bronchiectasis. Clinical features of bronchiectasis and results of spirometry, sputum microbiology and radiology were assessed and correlated., Results: Most patients had idiopathic bronchiectasis (74%) and did not have other significant disease. The dominant symptom was chronic productive cough present in 98% of patients with other important symptoms being chronic rhinosinusitis (70%), dyspnoea (62%), and fatigue (74%). Most patients had had a chronic productive cough for over 30 years prior to diagnosis and over 80% of patients had chronic respiratory symptoms from childhood. The dominant finding on physical examination was the presence of crackles which were generally bi-basal. Spirometry showed mild airway obstruction with an average forced expiratory volume in 1s of the cohort of 76% predicted. Radiologic imaging generally showed multilobar disease (80%)., Conclusions: The typical profile of bronchiectasis in this group of patients was of longstanding productive cough, rhinosinusitis and fatigue in non-smokers with crackles on chest auscultation.

Airway pathologies have been comprehensively researched in adult asthma, but in children, the extent of airway inflammation associated with episodic wheeze, often diagnosed as asthma, has not been fully characterized. It is not clear whether persistent airway inflammation is present in the absence of wheezing symptoms, and there is controversy regarding the role of age and atopy. This study assessed cellular and cytokine markers of airway inflammation in asymptomatic children with a history of episodic wheeze. Children with a history of episodic wheeze and cough (study group) and nonasthmatic patients requiring elective surgery (control group) were recruited. All subjects in the study group had a history of significant episodic wheezing (>2 episodes per year), and used only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control group). Differential cell counts of BAL and flow cytometry were performed to identify T-lymphocyte phenotypes, and intracellular cytokine profiles were measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T-cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and 21 nonasthmatic subjects without respiratory symptoms were recruited. Study and control subjects were matched for age (median age, 5 years) and demographic characteristics. Study subjects had higher IgE levels, but their measurements were still within normal range. No significant differences in BAL differential cell counts were noted, and in both groups, the majority of T-cells were CD3+ CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4, IL-5, and IL-10. The results of this study suggest that significant T-cell-driven airway inflammation is absent in mild or nonatopic, asymptomatic children of this age group who have episodic wheeze. Our findings support asthma management guidelines that do not recommend long-term treatment of this group of patients with anti-inflammatory medications., (Copyright 2006 Wiley-Liss, Inc.)

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P<0.05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P<0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis.

Vascular participation manifested by a runny nose (rhinorrhea) is a prominent feature of the acute consequences of rhinovirus infection. Vascular endothelial growth factor (VEGF) is an angiogenic factor that also induces potent increases in vascular permeability; it is a candidate mediator of rhinorrhea in response to rhinovirus infection as well as contributing to enhanced vascular leakage in rhinovirus-linked asthma exacerbations. It has been shown that rhinovirus induces significant increases in both VEGF protein and mRNA in primary airway fibroblasts [Ghildyal et al. (2005): J Med Virol 75:608-615]. The current studies assessed VEGF responses to rhinovirus in primary culture airway epithelium, in epithelial and fibroblast cell lines and in rhinovirus-infected nasal secretions. Epithelial and fibroblast cells were infected with rhinovirus serotype 16 and VEGF protein and isoforms assessed by ELISA and RT-PCR, respectively. VEGF protein was released by both epithelial and fibroblast cell lines and primary airway epithelial cells in culture but was not increased following rhinovirus infection. PCR products coding for four or five of the six known VEGF isoforms were produced (121, 145, 165 and 183, and/or 189 amino acids) in cell lines and primary culture cells, but no specific isoform was linked to rhinovirus infection. Nasal VEGF was also measured in a cohort of asthmatics with verified rhinovirus and respiratory syncytial virus (RSV) infection. VEGF was not raised following rhinovirus infection alone, but was increased significantly if concomitant RSV infection was present. The data suggest that fibroblasts rather than the epithelium may play a key role in VEGF mediated vascular responses after rhinovirus infection. This may aid recruitment of inflammatory cells and contribute to airway inflammation and bronchial obstruction., (Copyright 2006 Wiley-Liss, Inc.)

Diagnosis of infection with Mycobacterium tuberculosis (MTB) using tuberculin skin testing (TST) is often hampered by prior Bacille Calmette-Guérin (BCG) vaccination. ESAT-6 is a protein that is expressed by MTB but absent in BCG. It has been postulated that it might be useful in distinguishing MTB-specific immune responses. This study measured CD4 T cell responder frequencies specific for ESAT-6 and the TST reagent purified protein derivative (PPD) in patients with tuberculosis (n = 16), controls with non-tuberculous pneumonia (n = 8) and normal subjects (n = 7). Responses were identified using the intracellular cytokine staining technique and flow cytometry on whole blood samples, and performed blinded to the patient condition. Antigen-specific CD4 cells were defined by CD69 positivity and one or more cytokine [interleukin (IL)-2, IL-4, IL-10, interferon (IFN)-gamma] and/or CD40L positivity. With ESAT-6 stimulation it was found that TB patients had significantly higher frequencies of IFN-gamma and CD40L-positive CD4 T cells compared to the normal group, while no significant differences were measured with PPD stimulation. A responder frequency of 0.01% or higher for at least one of the measured cytokines/CD40L was defined as a positive response. Using this criterion to compare the two patient groups, PPD had 100% sensitivity but 0% specificity while ESAT-6 had 100% sensitivity and 88% specificity. Use of MTB-specific proteins such as ESAT-6 in combination with intracellular cytokine staining and flow cytometry has the potential to identify individuals with MTB infection.

Objective: A retrospective case-control study at Monash Medical Centre (MMC), a tertiary referral hospital in Melbourne, Australia, was conducted to identify risk factors associated with very severe asthma in paediatric patients., Methodology: Asthmatics admitted to an intensive care unit (ICU; n=52) were identified and considered to represent cases of very severe/near fatal asthma (NFA group). This group was compared to asthmatics who had been admitted on one occasion only to the emergency department at MMC (non-NFA controls, n=53). Patient files were examined and factors that may be linked to NFA were recorded. Information not on file was obtained from patients/parents during a structured telephone interview. Data for the two groups were compared, univariate and multivariate logistic regression analyses were performed, and odds ratios (OR) were calculated., Results: Univariate analysis indicated that asthmatics with NFA were more likely to be older (P=0.01) and have a longer duration of asthma (P=0.02). They were also more likely to have hay fever (P=0.002; OR, 7.6), use inhaled corticosteroids (P=0.001), long acting beta(2) agonists (P=0.02), have an asthma management plan (P=0.006), and see a respiratory specialist (P=0.001). Parental smoking habits were not different between the groups. Multivariate logistic regression analysis identified male gender (P=0.05; OR, 5.7) and use of inhaled corticosteroids (P=0.07; OR, 7.2) as factors that may be predictive of NFA., Conclusions: This study identifies a number of factors associated with NFA; many are similar to those reported in adult patients. Asthma severity explains some findings, but the data also suggest that additional independent risk factors such as gender and duration of asthma may operate in children.

The events linking rhinovirus (RV) infection to airway symptoms are poorly understood. The virus initially infects airway epithelium followed by a vigorous inflammatory response that may entail spread of RV from epithelium to other cells in the airway wall. However, RV has fastidious growth characteristics and to date reproductive infection of primary cells other than human airway epithelium has not been confirmed. Airway fibroblasts are adjacent to and in contact with epithelial cells, play a key role in innate immune responses, and may participate in the evolution of inflammation. To investigate fibroblast actions, we first determined whether RV could infect and replicate in primary culture human lung fibroblasts. RV serotype 16 (RV16) was used to infect fibroblasts grown from lung tissue, and virus infection with replication was demonstrated by a combination of techniques. RT-PCR was used to show an increase in RV transcription; confocal microscopy demonstrated colocalization of the replicative form of RV genome (double-stranded RNA) and RV16 proteins; infectious virus was also recovered from the culture supernatant of infected fibroblasts. Functional consequences of RV infection were next examined. RV infection of fibroblasts was followed by an increase in epithelial neutrophil-activating peptide-78 (ENA-78) mRNA and protein. The permeability factor vascular endothelial growth factor (VEGF) was also induced over a similar time course. These data suggest that interactions between RV and human fibroblasts are feasible, may coordinate neutrophil chemoattraction with enhanced vascular permeability and that fibroblasts may contribute to inflammatory responses following RV infections., ((c) 2005 Wiley-Liss, Inc.)

The outcome in adult bronchiectasis has not been well described; in particular there has been a lack of long-term prospective studies. Therefore a follow-up study was performed to assess outcome in bronchiectasis in a cohort of adult patients. One hundred-and-one sequential adults, 33 male and 68 female; age 54 +/- 14 years (mean +/- SD) with bronchiectasis had a clinical assessment and spirometry performed. All were non-smokers and 84 were classified as having idiopathic disease. Patients were commenced on a standardized treatment regime and followed up for a minimum period of 2 years. On their last review when patients were clinically stable, a repeat clinical assessment and spirometry was performed and compared with the initial review. The primary endpoints measured were symptoms and FEV1. Subjects were followed up for 8.0 +/- 4.9 years. Clinical review showed that the patients had persistent symptoms that, in the case of dyspnea and sputum volume, were worse on follow-up. Spirometry showed a significant decline in FEV1 over the follow-up period with an average loss of 49 ml per year. This study showed in this group of predominantly female adult patients with bronchiectasis followed up for 8 years, patients had persistent symptoms and an excess loss in FEV1.

Nontypeable Haemophilus influenzae (NTHi) colonizes the upper respiratory tract of most healthy people and is also a major cause of infection in chronic obstructive lung disease. The immune response to this bacterium has not been well characterized. We tested the hypothesis that recurrent airway infection with NTHi may be associated with nonclearing adaptive immunity. Study subjects were healthy control subjects and patients with idiopathic bronchiectasis who had severe chronic infection with H. influenzae. We established that all subjects in both groups had detectable antibody to NTHi, suggesting that most normal people have developed an adaptive immune response. To characterize the nature of the immune response, we measured antigen-specific production of T helper cell cytokines and CD40 ligand by flow cytometry and immunoglobulin subclass levels in peripheral blood. We found that normal control subjects made Th1 response to NTHi with distinct CD40 ligand production. In contrast, subjects with bronchiectasis had predominant production of Th2 cytokines, decreased expression of CD40 ligand, and different immunoglobulin G subclass production. Therefore, chronic infection with NTHi in bronchiectasis is associated with a change in adaptive immunity that may be important in the pathogenesis of bronchial infection.

Indirect tests of bronchial responsiveness to agents such as adenosine 5'-monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti-inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double-blind study design the effect of 400 micrograms/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pretreatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges. Compared with placebo-treated subjects, FEV1 increased significantly in the children receiving BDP. This improvement was observed in those randomized to either the AMP challenge or the bradykinin challenge. In children challenged with AMP, the PD20 AMP increased significantly after 1 month and 2 months of BDP therapy when compared with placebo, while under similar conditions the PD20 methacholine was not significantly affected. In children challenged with bradykinin, BDP therapy did not significantly alter either the PD20 bradykinin or PD20 methacholine. We conclude that a bronchial challenge with AMP appears to be a more sensitive predictor of response to anti-inflammatory treatment than either methacholine or bradykinin.

Background: Respiratory symptoms such as cough and wheeze are associated with significant morbidity, including school absenteeism., Methods: A respiratory questionnaire was sent to the parents of all 5727 children aged 7-9 years of age registered with 95 general practitioners in the Southampton area to determine (a) the prevalence of asthma, cough and wheeze, (b) the effects of respiratory symptoms on school absenteeism, and (c) the use of anti-asthma medication., Results: A total of 4830 parents replied (response rate 86%). The 12 month prevalence of wheeze in the absence of cough was 5.5%, cough in the absence of wheeze was 10.0%, and 7.6% reported cough and wheeze; 15.2% of children had been diagnosed. Of the 4830 who replied, 12.7% were receiving bronchodilators, 0.6% xanthine derivatives, 1.7% sodium cromoglycate, and 4.1% inhaled corticosteroids. In all, 348 (7.2%) children had missed more than five days of schooling in the preceding year for respiratory symptoms, while 43 children (0.9%) had missed more than 20 days of schooling in the preceding year. Of the children who had missed more than five days of schooling, 43% reported cough and wheeze, 33% cough alone, and 16% wheeze alone in the preceding year. Compared with children who coughed, those who wheezed were significantly more likely to be diagnosed as asthmatic and to be receiving bronchodilators or inhaled corticosteroids., Conclusions: In this study, cough was the most frequently reported symptom amongst children missing more than five days of schooling per year.

Objective: To study the postoperative outcome of infants under the age of 18 months in whom an adenotonsillectomy had been performed, with particular emphasis on the pre- and postoperative weight gain and linear growth velocities, and the resolution of symptoms of obstructive sleep apnoea (OSA)., Methodology: A retrospective study of all infants in whom an adenotonsillectomy had been performed during the 5 year period to January 1990. Details of pre- and postoperative outcome variables were obtained by review of hospital and office records and by telephone calls to the parents., Results: Complete data were available for 29 (76%) of the 38 infants in whom an adenotonsillectomy had been performed. The data from these infants are reported. Pre-operatively, all infants had clinical symptoms of OSA, and 52% of infants also presented with failure to thrive (FTT). Seven infants were dysmorphic: three had Down syndrome, three had a craniofacial anomaly and one infant had Mobius syndrome. Following adenotonsillectomy, 23 infants (79%) had complete resolution of their OSA symptoms. Two infants with Down syndrome required a tracheostomy to relieve persistent upper airway obstruction. Eighty-seven per cent of the infants with pre-operative FTT had a significant increase in weight gain velocity postoperatively (mean 195.1 +/- 80.8 s.d. vs 509.8 +/- 249.1 g/month; P < 0.001), including the infants with mild persistent symptoms of OSA. The weight gain velocity of infants who were not failing to thrive pre-operatively did not change significantly following adenotonsillectomy (328.1 +/- 106.9 vs 333.2 +/- 146.4 g/month; P = 0.82). The linear growth velocity of all infants did not change significantly postoperatively., Conclusions: OSA should be considered in infants with FTT, as adenotonsillectomy is an effective treatment for OSA in infancy, and the weight gain velocity of these infants may increase significantly postoperatively. Overnight oximetry or other physiological studies may be required if the clinical signs and symptoms of OSA are equivocal.

Poorly controlled severe asthma can lead to growth impairment in childhood. In children with mild asthma, it is less clear whether treatment influences growth or adrenal function. We determined in a randomized, double-blind, placebo-controlled, community-based study, the effect of inhaled beclomethasone dipropionate (BDP) 400 micrograms/day for 7 mo on the linear growth and adrenal function of 94 children 7 to 9 yr of age. Height was measured at least monthly during treatment, and adrenal function assessed by overnight urinary cortisol at baseline and after 3 and 6 mo of treatment. Mean regressed daily growth was significantly decreased during the treatment period in the BDP-treated group, 0.79 versus 1.14 mm/wk (difference 0.35 mm/wk; 95% CI -0.46 to -0.25; p < 0.0001). At the end of the 7 mo, the BDP-treated children had grown significantly less than the children on placebo: mean of 2.66 versus 3.66 cm (difference 1.0 cm; 95% CI -1.36 to -0.64 cm; p < 0.0001). Growth was significantly decreased in both males and females. During a washout period of 4 mo, there was no significant catch-up growth. BDP had no effect on overnight urinary cortisol production. BDP at a dose taken by many children significantly decreases statural growth in children with mild asthma, and this effect is unlikely to be mediated through the hypothalamo-pituitary-adrenal axis.

Conventional methods for measuring respiratory mechanics model the respiratory system as a single compartment. The interrupter technique allows the respiratory system to be considered as a two compartment model with "flow resistance" of the conducting airways (Rinit), calculated from the initial pressure drop (Pinit), considered separately from Pdiff, as a measure of the viscoelastic properties of the lung and chest wall and any pendelluft present. The pulmonary mechanics of 50 intubated and mechanically ventilated preterm infants (< or = 1500 g) were studied during the first week of life using conventional methods and the interrupter technique to determine whether it was possible to predict which infants would develop bronchopulmonary dysplasia (BPD). Pulmonary mechanics of preterm infants intubated and ventilated for apnea of prematurity were also studied. The dynamic compliance of the respiratory system (Crsdyn) was significantly lower on day 1 (P < 0.001) and during the first week of life in the infants with HMD who developed BPD (ANOVA, P < 0.0001). There was no significant difference in the respiratory system resistance (Rrs), Rinit, or Pdiff between BPD and no-BPD groups. However, Pdiff was significantly higher in infants with HMD, regardless of the outcome, when compared to the infants ventilated for apnea of prematurity. This suggests that the pathology of HMD is distal to the conducting airways and significantly alters the viscoelastic properties of the lung on day 1. Using stepwise logistic regression Crsdyn on day 1 and birth weight or gestational age were significant independent predictors or the development of BPD, correctly classifying 92% of infants.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of the viscoelastic properties of the tissues of the respiratory system has recently been recognized, and lung models have been produced to describe the resistive and viscoelastic properties of the lung. The pulmonary mechanics of 10 rabbits were studied using the interrupter technique to assess the effect of volume history on the resistive and viscoelastic elements of the respiratory system. The influence of the tone of the muscles of respiration was also studied. In healthy lungs, the resistive and viscoelastic elements of the lung are dependent on the volume history of the respiratory system and are significantly lower if these elements do not reach a resting position before expiration. The chest wall made a significant contribution to the resistive and viscoelastic elements of the respiratory system, which was also dependent on the lung volume history. The tone of the muscles of respiration had no effect on the resistive or viscoelastic elements of the respiratory system.

The relationship between respiratory mechanics, changes in pulmonary blood flow (PBF), pulmonary arterial pressure, and left atrial pressure is unclear. Conventional methods for the measurement of respiratory mechanics model the respiratory system as a single compartment, which may not adequately represent the respiratory system in a diseased state. The interrupter technique models the respiratory system as two compartments, with the "flow resistance" of the conducting airways and chest wall (Raw) considered separately from Pdif, a measure of the viscoelastic properties of the lung and chest wall, together with any pendelluft present. The respiratory mechanics of 15 infants in the first year of life were studied during cardiac catheterization with the use of conventional methods and the interrupter technique. The infants had a PBF-to-systemic blood flow ratio ranging from 0.6 to 4.0:1. The specific dynamic compliance of the respiratory system was not related to the PBF; however, there was a significant relationship between PBF and the total resistance of the respiratory system (Rrs) [analysis of variance (ANOVA) F = 5.69, P < 0.05], Raw (ANOVA, F = 12.30, P < 0.01), and Pdif (ANOVA, F = 3.79, P < 0.05). Rrs increased significantly with an increase in mean left atrial pressure (ANOVA, F = 6.92, P < 0.05); however, dynamic compliance, Raw, and Pdif did not. These results suggest that the relationship between Rrs and PBF is due an increase in the resistive properties of the conducting airways and tissue components.

Deciding when to wean neonates from extracorporal membrane oxygenation (ECMO) can be difficult. The usefulness of simple measurements of pulmonary mechanics e.g., dynamic compliance (Cdyn) has been questioned. We investigated the pulmonary mechanics of eight neonates using the interrupter technique, which allows the partitioning of pulmonary mechanics into compartments representing the conducting airways and more peripheral phenomena (viscoelastic properties and "pendelluft"). Three neonates required ECMO for a congenital diaphragmatic hernia (CDH), two for hyaline membrane disease (HMO), two for meconium aspiration syndrome (MAS), and one for pneumonia. All neonates with MAS, HMD, and pneumonia were successfully weaned from ECMO when their Cdyn was 0.3 mL/cmH2O/kg or greater [mean 0.34 +/- 0.06 (SEM)]. All three neonates with CDH died and their highest Cdyn was 0.21, 0.19, and 0.09 mL/cmH2O/kg respectively (mean, 0.16 +/- 0.037). The airway resistance (Raw) and the slower component of pressure change after interruption (delta Pdiff), a measure of the more peripheral phenomena of the lung, were not significantly different in those neonates who survived and those who did not. The values for delta Pdiff in all patients were higher than those in healthy neonates. However, the Raw was not different. This suggests that the major disturbance in pulmonary mechanics was distal to the conducting airways. Those neonates who were successfully weaned from ECMO had a significantly higher Cdyn 24-48 hours prior to decannulation. Considering the lung as a two-compartment model offers no advantages when compared to the one-compartment model for the prediction of the outcome of a neonate on ECMO.

During the 10-yr period beginning January 1979, 59 infants and children with Guillain Barré syndrome (GBS) were admitted to our hospital. Tracheostomies were performed in 15 patients and their records were reviewed. Fourteen patients were recalled for assessment of pulmonary function and respiratory muscle strength (RMS). The median duration of assisted ventilation (including endotracheal [ET] intubation) was 21 days and the median duration of tracheostomy was 39 days. Only two patients were discharged with the tracheostomy in situ. All patients were successfully decannulated at the first attempt. No tracheostomy-related complications or symptoms were reported apart from croup in two patients. On review, lung volumes and maximal inspiratory and expiratory flows were normal. There was no evidence of tracheal stenosis or significant tracheomalacia. RMS tests were normal. In this hospital, tracheostomy is a safe, well-tolerated procedure in the management of infants and children with GBS who need long-term ventilation. There were no deaths and all patients returned to their normal school or were gainfully employed after their illness, although 12 patients had mild persistent weakness of at least foot dorsiflexion.

The records of all children who had a tracheostomy performed over a 10 year period from January 1979 were reviewed. Altogether 142 patients aged 1 day to 24.8 years received a tracheostomy, 70 in the first year of life. The conditions necessitating tracheostomy were trauma (n = 21), acquired subglottic stenosis (n = 21), subglottic haemangioma (n = 16), Guillain-Barré syndrome (n = 14), Pierre Robin syndrome (n = 9), craniofacial disorders (n = 9), micrognathia (n = 5), and others in 47. In patients successfully decannulated the median period of tracheostomy was 104 days (range 3 days to 9.0 years) and in 25 patients the tracheostomy is still in situ. Eighty four patients (60%) were discharged from hospital with their tracheostomy in situ and no patient was kept in hospital because of a tracheostomy beyond four weeks. There were two tracheostomy related deaths in hospital. Both patients had severe acquired subglottic stenosis secondary to ventilation for lung disease of prematurity. There were no tracheostomy related deaths at home; complications included tracheal granulomas and polyps (n = 19). After removal of the tracheostomy 13 children had a fistula requiring surgical closure and four required revision of the tracheostomy scar. Tracheostomy is well tolerated in small children, with few complications and can be managed safely in the home by the family.