Background: Estimating the probability of an asthma patient’s response to long-acting beta-2 adrenergic receptor agonists (LABA) from only a few lung function measurements would help clinicians avoid unnecessary drug prescription, contributing to personalized treatment and reduced costs. Aims and objectives: To develop a computational methodology capable of generating estimates of the probability of LABA-responsiveness and assess its accuracy using cohort data. Methods: Using fluctuation-based clustering (Delgado-Eckert E. et al. Thorax 2018; 73.2:107-115) we retrospectively analysed time series of PEF measurements recorded by 79 mild-to-moderate asthmatic adults during the placebo phase of a study aimed at characterizing the effects of salmeterol and salbutamol treatment (described in Thamrin C. et al. Eur Respir J 2009; 33:486–493). This yielded three clusters of patients: 1, composed mainly of salmeterol responders; 2, mainly non-responders; 3, a mixed group. We randomly removed 99% of the data from each time series, using these stripped-down versions as proxies for new patients’ data. Using Softmax Regression, we calculated the probability that a patient would be assigned to one of the three clusters. Based on the proportion of responders in each cluster, we calculated the salmeterol-responsiveness probability of a given “new” patient. We used a Receiver Operating Characteristic (ROC) curve to assess the probability’s classification performance. Results: The LABA-responsiveness probability ROC curve had a mean area under the curve of 0.7. Conclusion: Our method yields LABA-responsiveness probability estimates with good discriminatory power.

BACKGROUND:Despite reports of positive associations between paracetamol and asthma, the nature of these associations is unclear.OBJECTIVE:We aimed to investigate the associations between infant and childhood paracetamol use and atopy and allergic disease at 5-6 years.METHODS:In a birth cohort study, we collected reported paracetamol exposure between birth and 15 months in Christchurch (n=505) and between 5 and 6 years for all participants (Christchurch and Wellington) (n=914). Outcome data for reported current asthma, reported wheeze and atopy (measured using skin prick tests) were collected at 6 years for all participants. Logistic regression models were adjusted for potential confounders, including the number of chest infections and antibiotic use.RESULTS:Paracetamol exposure before the age of 15 months was associated with atopy at 6 years [adjusted odds ratio (OR)=3.61, 95% confidence interval (CI) 1.33-9.77]. Paracetamol exposure between 5 and 6 years showed dose-dependent associations with reported wheeze and current asthma but there was no association with atopy. Compared with use 0-2 times, the adjusted OR (95% CI) were wheeze 1.83 (1.04-3.23) for use 3-10 times, and 2.30 (1.28-4.16) for use >10 times: current asthma 1.63 (0.92-2.89) for use 3-10 times and 2.16 (1.19-3.92) for use >10 times: atopy 0.96 (0.59-1.56) for use 3-10 times, and 1.05 (0.62-1.77) for use >10 times.CONCLUSION AND CLINICAL RELEVANCE:Our findings suggest that paracetamol has a role in the development of atopy, and the maintenance of asthma symptoms. Before recommendations for clinical practice can be made, randomized-controlled trials are needed to determine whether these associations are causal.

BACKGROUND:In general, studies reporting positive associations between antibiotic exposure and respiratory and allergic disease have been unable to determine the nature of this association.OBJECTIVE:To examine the association between antibiotic exposure in infancy and the development of asthma, eczema and atopy in early childhood.METHODS:In a birth cohort study, we collected reported antibiotic exposure before 3 months and before 15 months along with outcomes (wheeze, asthma, eczema, rash, inhaler use) at 15 months (n=1011) and 4 years (n=986). Atopy was measured using skin prick tests at 15 months.RESULTS:We found significant univariate associations of antibiotic exposure before 3 months with asthma developing between birth and 15 months [OR 2.32 (95% CI 1.45-3.69)]. After adjustment for chest infections, this association reduced (OR=1.58, 95% CI 0.96-2.60) becoming marginally significant (P=0.07). A marginally significant association of antibiotics with atopy (OR=1.44, 95% CI 0.96-2.14) in the univariate analysis also reduced after adjustment for chest infections (OR=1.36, 95% CI 0.91-2.05). There was no effect of antibiotic exposure before 15 months on asthma developing after 15 months and present between 3 and 4 years (OR=1.35 95% CI 0.85-2.14). Antibiotic exposure before 3 months was not associated with eczema and rash developing between birth and 15 months but exposure before 15 months was related to eczema [OR 1.83 (95% CI 1.10-3.05)] and rash [OR 1.61 (95% CI 1.02-2.53)] developing after 15 months and remaining present at 4 years. These effects reduced in the multivariate analysis.CONCLUSIONS:Our findings suggest that the effect of antibiotics on respiratory disease may be due to confounding by chest infections at an early age when asthma may be indistinguishable from infection.

Respiratory symptoms are often used as the only diagnostic criteria for asthma in epidemiological surveys and the clinical diagnosis of asthma relies primarily on a detailed history. The aim of this study is to predict the diagnostic value of 11 different respiratory symptoms to diagnose asthma, and to determine if bronchial hyperresponsiveness (BHR) improves the predictive value of these respiratory symptoms.A random sample of 1257 subjects aged 20-44 years old in 3 different areas of New Zealand were selected between March 1991 and December 1992 to answer the European Community Respiratory Health Survey questionnaire on respiratory symptoms. Of these, 784 underwent bronchial challenge with methacholine. The prevalence of current doctor diagnosed asthma (DDA) defined as asthma confirmed by a physician and an asthma attack in the last 12 months was 8.3%. Wheezing with dyspnoea is the single best predictor of diagnosed asthma with a sensitivity of 82%, a specificity of 90% and a Youden's index of 0.72. Wheezing alone is more sensitive (94%) but less specific (76%), with a Youden's index of 0.70. The addition of BHR to asthma symptoms decreases sensitivity and increases specificity with a small increase in Youden's index to 0.75. In New Zealand adults, a history of wheezing with BHR best predicts a diagnosis of asthma but wheezing atone or with dyspnoea are the two best symptoms for predicting asthma. (c) 2006 Elsevier Ltd. AtI. rights reserved.

The gut microbiota may be important in the postnatal development of the immune system and hence may influence the prevalence of atopic diseases. Bifidobacteria are the most numerous bacteria in the guts of infants, and the presence or absence of certain species could be important in determining the geographic incidence of atopic diseases. We compared the fecal populations of bifidobacteria from children aged 25 to 35 days in Ghana (which has a low prevalence of atopy), New Zealand, and the United Kingdom (high-prevalence countries). Natal origin influenced the detection of bifidobacterial species in that fecal samples from Ghana almost all contained Bifidobacterium infantis whereas those of the other children did not. Choosing species on the basis of our bacteriological results, we tested bifidobacterial preparations for their effects on cell surface markers and cytokine production by dendritic cells harvested from cord blood. Species-specific effects on the expression of the dendritic-cell activation marker CD83 and the production of interleukin-10 (IL-10) were observed. Whereas CD83 expression was increased and IL-10 production was induced by Bifidobacterium bifidum, Bifidobacterium longum, and Bifidobacterium pseudocatenulatum, B. infantis failed to produce these effects. We concluded that B. infantis does not trigger the activation of dendritic cells to the degree necessary to initiate an immune response but that B. bifidum, B. longum, and B. pseudocatenulatum induce a Th2-driven immune response. A hypothesis is presented to link our observations to the prevalence of atopic diseases in different countries.

AIMS:To investigate the use of the Hospital Anxiety and Depression Scale (HADS) with recuperating chronic obstructive pulmonary disease (COPD) patients. To study prevalence rates and changes in clinically relevant anxiety and depression during rehabilitation.METHODS:Consecutive patients admitted to a non acute respiratory ward over a twelve week period were asked to complete a HADS questionnaire on three occasions. Nurses recorded basic demographic information on admission. Additional demographic, medical and psychiatric data were obtained by retrospective review of medical records.RESULTS:Of 93 consecutive inpatients, 79 (85%) completed the admission HADS. 72 patients were eligible to complete the day three HADS and 60 the discharge HADS. Clinically relevant anxiety (HADS score of > or =8) was indicated in 39 patients (50%) and depression in 22 (28%). HADS anxiety (p=0.05) and total scores (anxiety+depression) (p=0.03) decreased between admission and discharge. A larger proportion of patients scored within the normal or mild psychopathology range by discharge. More severe COPD (FEV1% predicted) correlated with higher HADS anxiety scores (r=-0.39, p<0.001) and HADS depression scores (r=-0.34, p<0.005). Patients with a recorded history of anxiety (p<0.0001) and depression (p<0.02) had higher WADS scores. Females (n=37) when compared to males (n=42), recorded significantly higher HADS anxiety scores throughout (p<0.005).CONCLUSIONS:Clinically relevant anxiety, indicated by higher HADS scores, was more common in patients with severe COPD, a past history of anxiety or depression and females. Anxiety and total mood improved during inpatient rehabilitation. The use of this instrument with New Zealand COPD patients may improve identification and treatment of anxious and depressed patients.

Aims. To prospectively record current epidemiology and microbiology of community-acquired pneumonia in two New Zealand centres.Methods. Between July 1999 and 2000 all adults admitted to Christchurch and Waikato Hospitals with community-acquired pneumonia were screened for study inclusion. All those enrolled had their medical history, clinical variables, inpatient management and clinical outcomes recorded and standardised microbial diagnostic testing carried out.Results. 474 participants were enrolled with a mean age of 64 years and a microbial diagnosis was made in 197 cases (42%). Streptococcus pneumoniae (14%), Haemophilus influenzae (10%) and Influenza A virus (7%), Legionella spp (4%) and Mycoplasma pneumoniae (3%) were the most commonly isolated organisms. An 'atypical' organism was diagnosed in 8% of cases compared to 30% and 23% in previous Christchurch and Waikato studies respectively. Fourteen of the 67 S pneumoniae isolates (21%) had reduced susceptibility to penicillin, all with a MIC less than or equal to 2 mug/mL, a level of reduced susceptibility not associated with worse patient outcomes. Clinical outcome included a mean hospital stay of 6.7 days and a 6 week mortality of 6%.Conclusion. Although S pneumoniae was the most commonly isolated organism in this study there have been significant changes in the prevalence of atypical organisms since previous surveys. Ongoing surveillance of antibiotic resistance and variations in the prevalence of organisms causing community-acquired pneumonia is required to guide clinicians' empiric antibiotic use.

AIMS To examine the prevalence of asthma symptoms, bronchial hyperresponsiveness (BHR) and atopy in a random population sample of New Zealand adults. METHODS A random sample of 2004 adults, aged 20-44 years, in Hawkes Bay, Wellington and Christchurch, were selected from respondents to a one-page respiratory screening questionnaire and invited to take part in further testing. Subjects attending the testing centres' laboratories underwent a detailed respiratory symptom questionnaire, Phazet testing to eleven common allergens, blood samples for total and specific IgE, and measurement of bronchial hyperresponsiveness. Subjects who did not wish to participate were encouraged to complete the questionnaire by telephone. RESULTS A participation rate of 67% (1257 of 1877 eligibles) was achieved. We found a high prevalence for all measures of asthma in the previous 12 months: wheezing was reported by 28.5%, waking with shortness of breath by 7.7%, a physician diagnosis of asthma by 15.9% and asthma medications were used by 8.5%. Bronchial hyperresponsiveness was found in 24.9%, atopy in 34.8% and elevated serum IgE levels in 30.5%. Asthma symptoms (in the past 12 months) and atopy decreased with increasing age, whereas bronchial hyperresponsiveness increased with age. Females reported higher prevalences of waking with coughing (45.9%), nasal allergies (43.5%) and skin allergies (48.8%) compared to males (30.5%, 31.9% and 37.0%, respectively). There were no significant regional differences. CONCLUSIONS Asthma symptoms, bronchial hyperresponsiveness and atopy are all common in adult New Zealanders. Their prevalence is associated with age, gender and current smoking but there are no significant regional differences between Hawkes Bay, Wellington and Christchurch.

Background: House dust mite allergens are a risk factor for asthma in New Zealand, and levels in domestic dwellings have been found to be high compared with levels in most other countries, Studies in other countries have demonstrated lower levels of Dermatophagoides pteronyssimus allergens in public places compared with levels in domestic dwellings.Objectives: The purpose of this study was to measure reservoir Her p I levels in public places in New Zealand and to examine determinants of these levels.Methods: Reservoir dust was obtained in the two centers (Christchurch and Wellington) from hotels, hospitals, rest homes, churches, primary schools, childcare centers, cinemas, bank head offices, and airplanes; samples were also obtained from ski lodges, Single measurements of temperature and relative humidity were taken with thermohygrometers and an average humidity over 2 weeks was estimated with use of waxed wooden sticks. Information was collected on building construction, type of heating, and frequency of cleaning. Der p 1 levels (micrograms per gram of fine dust) for Boor (n = 202), bed (n = 65), and seat (n = 24) samples in public places were expressed as geometric means (95% confidence intervals).Results: Der p 1 levels in public places were significantly lower than domestic levels in both Wellington and Christchurch. Both Boor and bed levels were higher in hotels than in other public places, After controlling for potential confounders, floor Der p 1 levels were higher with carpeted floors (p < 0.0001) and lower with recent cleaning (p = 0.02) and bed Her p 1 levels were higher with timber wall construction (p = 0.03). Other building, heating, or cleaning characteristics did not show significant associations with allergen levels.Conclusion: Der p 1 levels were much lower in public places than in domestic dwellings with floor levels primarily affected by floor covering.

The objectives of this study were to measure the population prevalence of symptoms of chronic obstructive lung disease and mild airway obstruction and to compare these between occupational groups. There were 1,609 subjects (63.9% response rate) who completed a respiratory questionnaire. Of these, 1,132 (70.4%) underwent pulmonary function testing (FEV1 and FVC). Twenty-one categories of current occupation were used for analysis. Four definitions of chronic obstructive pulmonary disease (COPD) were used: (1) chronic bronchitis, (2) chronic bronchitis with airway obstruction, (3) shortness of breath, and (4) shortness of breath with airway obstruction. For chronic bronchitis, adjusted prevalence odds ratios were significantly elevated for food processors other than bakers (OR = 2.83; 95% CI, 1.27 to 6.29) and chemical processors (OR = 18.84; 3.71 to 95.64). The combination of chronic bronchitis and mild airway obstruction (FEV1/FVC < 0.75) was associated with bakers (OR = 25.5; 3.86 to 168.53) and spray painters (OR = 14.40; 2.85-72.69). Shortness of breath was associated with hairdressers (OR = 2.75; 0.80 to 9.42) and bakers (OR = 6.72; 0.57 to 79.66), and nursing was associated with lower levels of shortness of breath (OR = 0.42; 0.16 to 1.15). Working ever with vapors, gases, dust, or fumes was significantly associated with chronic bronchitis and airway obstruction (OR = 3.13; 1.07 to 9.12). This population-based study has identified certain occupations with increased prevalence of chronic bronchitis and COPD.

Aim. In response to community concern about the possible respiratory effects of emissions from a fertiliser plant, a study was carried out to determine whether the prevalence of asthma symptoms in 5-8 yr old children in an industrial suburb of Christchurch (Hornby) was the same as in the rest of Christchurch.Methods. A sample of 646 children aged 5-8 years in Hornby was compared with 1183 6-7 year old children randomly selected from schools throughout the Christchurch metropolitan area. The Christchurch sample was part of the International Study of Asthma and Allergies in Childhood (ISAAC) carried out during 1993. ISAAC questionnaires on respiratory symptoms with some additional questions about smoking and pets were answered by the caregivers of the children sampled.Results. Response rates were 97% in Hornby and 94% in Christchurch. Of the sample, 29% (Hornby) and 27% (Christchurch) had 'wheeze in the last 12 months' while 45% of Hornby and 44% of Christchurch children had 'ever wheezed', 28% had 'ever had asthma'. Significantly more children in Hornby (44%) were exposed to passive smoking compared to Christchurch (29%). Indoor pets were present in 73% and 67% of homes, respectively.Conclusion. There was no evidence of an increase in asthma symptoms reported in children in the industrial area of Hornby.

AIMRecognition of heart failure may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction or obesity. In a previous study of patients with acute dyspnoea, we showed that the measurement of plasma brain natriuretic peptide (BNP)-a hormone secreted in increased amounts by the failing heart-accurately distinguishes heart failure from primary lung disorder. The aim of the present study was to develop a rapid assay for BNP and evaluate its diagnostic use in patients acutely hospitalised for increasing dyspnoea of any cause.METHODSA rapid assay for plasma BNP, providing results within 24 h of blood collection, was developed without loss of precision. The results of the rapid and previously established BNP assays were highly correlated (r = 0.9). To determine the diagnostic value of the rapid assay, measurements were undertaken on the day of admission in 123 breathless patients (mean age 68.3, range 23 to 90 years) and related to conventional diagnostic assessments and final outcome.RESULTSIn patients diagnosed and treated urgently for clinical heart failure, plasma BNP was significantly higher (115 (SE 13) pmol/L, n = 39) than in those without clinical heart failure (33 (5) pmol/L, n = 84, p < 0.001). Using a cut-off of 50 pmol/L for the presence of heart failure, there was discordance between BNP level and clinical diagnosis in 21 of 123 cases. Reassessment after independent analysis of discordant cases increased the difference in BNP level in the presence (123 (13) pmol/L, n = 43) or absence (24 (1.5) pmol/L, n = 80) of heart failure. Using two way analysis of variance, no further improvement in discrimination was found when chest radiographs were used together with the BNP data.CONCLUSIONRapid BNP assays are practicable and provide accurate information on cardiac status-superior to chest radiographs in many cases-early in the course of the patient's presentation with acute dyspnoea.

A standardised management protocol has been developed for the assessment and treatment of adults with acute asthma attending an emergency department. The management protocol consists of an assessment sheet for recording essential features of the history and examination findings and a flow diagram with guidelines for initial management that were based on spirometric recordings. The protocol was introduced at Wellington Hospital in 1986. The effect of this intervention was assessed by analysing emergency department records during the three months before and one year after the introduction of the protocol. The use of the assessment sheet improved history taking and led to the increased use of serial measures of airflow obstruction and improved documentation of follow up arrangements. The provision of management guidelines influenced the emphasis of management, including an increased use of corticosteroids intravenously and more frequent use of an additional dose of nebulised bronchodilator. In the light of the initial experience the protocol has been modified and its use either in an emergency department or in general practice is recommended.

Inhalation of nebulised water can provoke bronchoconstriction in asthmatic patients. In the first part of this study, a community survey identified that about 20% of patients with home nebulisers currently use water as a diluent. In the second part of this study, the airways effect of the use of water as a diluent for nebulised beta agonist was investigated. Nineteen asthmatic subjects were administered nebulised 2.5 mg salbutamol, diluted with either 2 mL water or physiological saline, and forced expiratory volume in one second (FEV1) was measured at baseline and at regular intervals for 45 minutes after nebulisation. Although there was a trend towards a reduced bronchodilator response with water as diluent, the differences between the two diluents were not significantly different. Paradoxical bronchoconstriction was not observed when salbutamol was diluted with water. We conclude that the common practice of diluting bronchodilator nebuliser solution with water does not result in a significant reduction in the overall bronchodilator response.

We reviewed the medical assessment and treatment of 108 consecutive adult asthmatic patients who attended the Wellington Hospital emergency department for treatment of asthma. Almost 90% of these patients were self referred. Systemic corticosteroids were administered or increased in dose during this asthma attack in only 14% of the 93 patients in whom prior drug therapy was recorded. In the emergency department measurement of either peak expiratory flow or forced expiratory volume in one second was made before treatment in 89% of patients, and after treatment in 77%. About 50% received systemic corticosteroids during their attendance, and of the 66 who were subsequently discharged, 40% were prescribed oral prednisone. Communication with general practitioners concerning patients discharged was poor. We conclude that although the medical assessment and management of severe asthma in this emergency department was of a high standard, there were problems relating to the increased reliance by asthmatic patients on this hospital based service.