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Background: The delivery of antipseudomonal antibiotics by inhalation to Pseudomonas aeruginosa-infected subjects with non-cystic fibrosis (CF) bronchiectasis is a logical extension of treatment strategies successfully developed in CF bronchiectasis. Dual release ciprofloxacin for inhalation (DRCFI) contains liposomal ciprofloxacin, formulated to optimise airway antibiotic delivery., Methods: Phase II, 24-week Australian/New Zealand multicentre, randomised, double-blind, placebo-controlled trial in 42 adult bronchiectasis subjects with ≥2 pulmonary exacerbations in the prior 12 months and ciprofloxacin-sensitive P aeruginosa at screening. Subjects received DRCFI or placebo in three treatment cycles of 28 days on/28 days off. The primary outcome was change in sputum P aeruginosa bacterial density to the end of treatment cycle 1 (day 28), analysed by modified intention to treat (mITT). Key secondary outcomes included safety and time to first pulmonary exacerbation-after reaching the pulmonary exacerbation endpoint subjects discontinued study drug although remained in the study., Results: DRCFI resulted in a mean (SD) 4.2 (3.7) log10 CFU/g reduction in P aeruginosa bacterial density at day 28 (vs -0.08 (3.8) with placebo, p=0.002). DRCFI treatment delayed time to first pulmonary exacerbation (median 134 vs 58 days, p=0.057 mITT, p=0.046 per protocol). DRCFI was well tolerated with a similar incidence of systemic adverse events to the placebo group, but fewer pulmonary adverse events., Conclusions: Once-daily inhaled DRCFI demonstrated potent antipseudomonal microbiological efficacy in adults with non-CF bronchiectasis and ciprofloxacin-sensitive P aeruginosa. In this modest-sized phase II study, DRCFI was also well tolerated and delayed time to first pulmonary exacerbation in the per protocol population.

Background and Aims: The clinical impact of nocturnal desaturation on health related quality of life (HRQL) and sleep in chronic obstructive pulmonary disease (COPD) has been little studied. The aim of this study was to evaluate the prevalence and clinical impact of nocturnal desaturation in a typical outpatient population with COPD., Patients and Methods: Between 2002 and 2005, consecutive patients with COPD attending outpatient services at the study centre underwent resting oximetry if they were not on domiciliary oxygen therapy. If their resting saturations were less than 95%, overnight pulse oximetry was performed. Significant nocturnal desaturation was defined as spending more than 30% of at least one of two nights with a saturation of less than 90%. The Chronic Respiratory Questionnaire (CRQ) and Short Form 36 (SF36) were used to assess HRQL, and the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Score (ESS) and Functional Outcomes of Sleep (FOSQ) questionnaires were used to assess sleep quality and daytime function., Results: Of 1104 patients, 803 underwent resting oximetry and 79 had resting oxygen saturations of less than 95%. Of these, 59 agreed to undergo overnight oximetry (mean age 70 years, forced expiratory volume in 1 s 37.2% predicted, resting Po(2) on air 8.9 kPa). Significant nocturnal desaturation was seen in 29 (49.2%) of the 59 subjects. Assuming the less hypoxic patients do not have nocturnal desaturation, the prevalence of nocturnal desaturation in the whole clinic population could be estimated at 4.8%. There were no significant differences in CRQ, SF36, PSQI, ESS or FOSQ scores for desaturators compared with non-desaturators., Conclusion: Significant nocturnal desaturation was common in patients with COPD with resting saturations of less than 95%, but was estimated to have a prevalence of less than 5% in the whole outpatient population. Nocturnal desaturation was not associated with impairment of HRQL, sleep quality or daytime function.

Background: Guidelines for long term oxygen therapy (LTOT) recommend increasing oxygen flow by 1 l/min overnight. A study was undertaken in patients with COPD on LTOT to determine the prevalence of overnight desaturation if the usual oxygen flow rate is not increased at night, whether resting oxygen saturation predicts overnight desaturation, and whether overnight desaturation correlates with health related quality of life (HRQL) and sleep quality., Methods: A cross sectional prospective study was performed on consecutive patients with COPD on LTOT attending our regional outpatient oxygen service. All patients fulfilled standard criteria for LTOT, had been established on LTOT at a flow to achieve resting oxygen saturations >90%, but had not been instructed to increase oxygen flow overnight. Overnight desaturation was defined as <90% for > or =30% of the night on either of two consecutive nights. HRQL was evaluated with the SF-36 Health Survey Questionnaire, Chronic Respiratory Questionnaire, and the Pittsburgh Sleep Quality Index., Results: Thirty eight patients (63% men) of mean (SD) age 73.5 (8.04) years and mean (SD) forced expiratory volume in 1 second 0.77 (0.35) l were evaluated. Overnight desaturation occurred in six (16%; 95% CI 4 to 27). Desaturators had mean (SD) resting oxygen saturation on room air of 88 (4.2)% compared with 90 (4.1)% in non-desaturators (p = 0.15), and corrected saturations of 93 (2.0)% versus 94 (2.0)% (p = 0.18). HRQL and sleep quality were poor but did not differ between desaturators and non-desaturators., Conclusions: Most patients did not exhibit overnight desaturation despite not increasing their LTOT prescription overnight. These results challenge the recommendation of routinely increasing overnight oxygen flow in patients receiving LTOT.

Background: Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule < or = 3 cm in diameter on initial chest radiography., Methods: Clinical, physiological, and outcome data on 114 patients with an SPN < or = 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later., Results: 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median kappa values 0.79-0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (kappa=0.33), rose with CT information (kappa=0.44), and increased further with the addition of the FNB data (kappa=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman's test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31-70%). FNB data contributed most to the benefit (p<0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy., Conclusion: Both CT and FNB make cost effective contributions to the clinical management of SPN < or = 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.

Background: Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. Adverse psychological factors are purported risk factors for asthma death and SLTA /near fatal asthma. A study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have specific adverse psychological factors., Methods: A case-control study was undertaken. Cases (n=77) were admitted to the intensive care unit with SLTA (mean (SD) pH 7.17 (0.15), PaCO(2) 10.7 (5.0) kPa). Controls (n=239) were admitted to general wards with acute asthma and were matched only by date of index attack. An interviewer administered questionnaire was undertaken 24-48 hours after admission. A random sample of community based asthmatics was recruited to provide normative data on asthmatics for comparison with cases and hospital controls., Results: The risk of SLTA increased with age (OR 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were controlled for in all further analyses. There was a high prevalence of psychological disorder in both cases and matched controls, but there was no difference in prevalence of caseness for anxiety or depression, total (or individual) life events in last 12 months, availability of general or disease specific social support, nor in any of the domains of the Attitudes and Beliefs about Asthma Questionnaire (emotional (mal) adjustment, doctor-patient relationship, stigma, self-efficacy). Cases (SLTA) were less likely to have had previous emotional counselling (25% v. 35%, p<0.05). However, when comparison was made with a community based group of asthmatic patients, those admitted to hospital with acute asthma (SLTA and hospital controls) had a higher prevalence of anxiety and depression, higher total life events, and higher prevalence of certain specific life events., Conclusions: There was considerable psychological morbidity generally (and anxiety specifically) in those admitted with acute asthma. Specific adverse psychological factors were not risk factors for SLTA, when comparison was made with those admitted to hospital with acute asthma, but adverse psychological factors were a risk factor for hospitalisation for acute asthma (including SLTA). Psychological risk factors for adverse events in asthma are dependent both on the type of event under study and the comparison group used.

Background: Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. A case-control study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have different sociodemographic and clinical characteristics, evidence of inadequate ongoing medical care, barriers to health care, or deficiencies in management of the acute attack., Methods: Seventy seven patients with SLTA were admitted to an intensive care unit (pH 7.17 (0.15), PaCO(2) 10.7 (5.0) kPa) and 239 matched controls (by date of index attack) with acute asthma were admitted to general medical wards. A questionnaire was administered 24-48 hours after admission., Results: The risk of SLTA in comparison with other patients admitted with acute asthma increased with age (odds ratio (OR) 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were controlled for in all subsequent analyses. There were no differences in other sociodemographic features. Cases were more likely to have experienced a previous SLTA (OR 2.04, 95% CI 1.20 to 3.45) and to have had a hospital admission in the last year (OR 1.86, 95% CI 1.09 to 3.18). There were no differences between cases and controls in terms of indicators of quality of ongoing asthma specific medical care, nor was there evidence of disproportionate barriers to health care. During the index attack cases had more severe asthma at the time of presentation, were less likely to have presented to general practitioners, and were more likely to have called an ambulance or presented to an emergency department. In terms of pharmacological management, those with SLTA were more likely to have been using oral theophylline (OR 2.14, 95% CI 1.35 to 3.68) and less likely to have been using inhaled corticosteroids in the two weeks before the index attack (OR 0.69, 95% CI 0.47 to 0.99). While there was no difference in self-management knowledge or behaviour scores, those with SLTA were more likely to have inappropriately used oral corticosteroids during the acute attack (OR 2.09, 95% CI 1.02 to 4.47)., Conclusions: In comparison with those admitted to hospital with acute severe asthma, patients with SLTA were indistinguishable on sociodemographic criteria (apart from male predominance), were more likely to have had a previous SLTA or hospital admission in the previous year, had similar quality ongoing asthma care, had no evidence of increased physical, economic or other barriers to health care, but had demonstrable deficiencies in the management of the acute index attack. Educational interventions, while not losing sight of the need for good quality ongoing care, should focus on providing individual patients with better advice on self-management of acute exacerbations.

The spectrum of nitrofurantoin lung injury continues to widen. The case histories are presented of two patients who developed lung disease associated with the use of nitrofurantoin with histological features of bronchiolitis obliterans organising pneumonia (BOOP), a rare but recognised form of drug induced injury. The two middle aged women presented with respiratory symptoms after prolonged treatment with nitrofurantoin. Both had impaired lung function and abnormal computed tomographic scans, and their condition improved when nitrofurantoin was withdrawn and corticosteroid treatment commenced. The favourable outcome in these two patients contrasts with the fatal outcome of the two other reported cases of nitrofurantoin induced BOOP. We suggest that the previous classification of nitrofurantoin induced lung injury into "acute" and "chronic" injury is an oversimplification in view of the wide variety of pathological entities that have subsequently emerged.

Background: An obstructive defect is usual in bronchiectasis, but the pathophysiological basis of airflow obstruction remains uncertain. High resolution computed tomographic (CT) scanning now allows quantitation of static morphological abnormalities, as well as dynamic changes shown on expiratory CT scans. The aim of this study was to determine which static and dynamic structural abnormalities on the CT scan are associated with airflow obstruction in bronchiectasis., Methods: The inspiratory and expiratory features on the CT scan of 100 patients with bronchiectasis undergoing concurrent lung function tests were scored semi-quantitatively by three observers., Results: On univariate analysis the extent and severity of bronchiectasis, the severity of bronchial wall thickening, and the extent of decreased attenuation on the expiratory CT scan correlated strongly with the severity of airflow obstruction; the closest relationship was seen between decreased forced expiratory volume in one second (FEV(1)) and the extent of decreased attenuation on the expiratory CT scan (R(s) = -0.55, p<0. 00005). On multivariate analysis bronchial wall thickness and decreased attenuation were consistently the strongest independent determinants of airflow obstruction. The extent of decreased attenuation was positively associated with the severity of bronchial wall thickness, but was not independently linked to gas transfer levels. Endobronchial secretions seen on CT scanning had no functional significance; the severity of bronchial dilatation was negatively associated with airflow obstruction after adjustment for other morphological features., Conclusions: These findings indicate that airflow obstruction in bronchiectasis is primarily linked to evidence of intrinsic disease of small and medium airways on CT scanning and not to bronchiectatic abnormalities in large airways, emphysema, or retained endobronchial secretions.

Background: Studies of asthma death and severe life threatening asthma (SLTA) include reports of patients who had rapid onset asthma. A study was undertaken to determine the relative frequency of rapid (< 6 hours duration) and slow (> or = 6 hours) onset attacks in patients admitted to hospital with acute severe asthma, and to establish whether those with rapid onset asthma differ in terms of risk factors for asthma morbidity and mortality such as indices of asthma severity/control, socioeconomic factors, health care, and psychological factors., Methods: A cross sectional study was performed on 316 patients aged 15-49 years admitted with acute severe asthma and interviewed within 24-48 hours of admission., Results: Patients underestimated the duration of the index attack. Only 27 (8.5%) were classified as rapid onset. There were more men in the rapid onset group than in the slow onset group (52% versus 26%), and there was evidence of socioeconomic advantage in the patients with rapid onset attacks. The rapid onset group had more previous episodes of SLTA and were more likely to present with SLTA, but there was no difference in length of stay in hospital. The rapid onset group were less likely to have presented to a GP during the index attack and were more likely to have used ambulance services. There was no difference between the groups in any psychological or health care measure., Conclusions: Rapid onset attacks are an important but uncommon manifestation of asthma that are more likely to present with SLTA in patients who are more likely to have had previous SLTA. Male subjects are at increased risk of rapid onset attacks, and socioeconomic disadvantage, deficiencies in health care (ongoing and acute), and psychological factors are no more common in these patients than in those with attacks of slow onset. These data are consistent with the hypothesis that there is a small proportion of patients with rapid onset severe asthma who do not have the usual risk factors associated with asthma morbidity or mortality, and thus require different management strategies.

Background: It is hypothesised that, despite recent initiatives to improve asthma self-management including asthma education, detailed investigation of the sequence of events culminating in hospital admission will lead to the identification of important management errors and thus the likelihood that the majority of severe asthma attacks are preventable by currently available strategies, and that psychological, health care and socioeconomic factors are risk factors for such management errors., Methods: A cross sectional study was undertaken of 138 patients aged 15-50 years admitted to hospital (general ward or intensive care unit) with acute severe asthma who were assessed within 24-72 hours of admission using a number of previously validated instruments. A detailed history of events of the attack was assessed against predetermined criteria for non or delayed use of oral corticosteroids and non or delayed use of emergency ambulance services., Results: Subjects had evidence of severe chronic asthma and had acute severe asthma at presentation (n = 90, pH = 7.3 (0.2), PaCO2 = 7.2 (5.0) kPa) but duration of hospital stay was short (3.7 (2.6) days). Serious management errors occurred very frequently and most were deemed to have been made by the patient. Forward stepwise regression revealed that delayed or non-use of oral corticosteroids was predicted independently by lack of paying job (p = 0.02), high total use of inhaled beta agonists in the 24 hours before index admission (p = 0.04), loss of a job in the last year (p = 0.04), low frequency of use of oral corticosteroids in the last year (p = 0.06), concerns during the index attack about medical expenses (p = 0.07), and delay in the use of ambulance services (p = 0.05)--the model being responsible for 23% of the variance. Delayed or non-summoning of emergency ambulance services was predicted independently by total life events (p = 0.03), having something stolen in the last year (p = 0.003), panic during the index attack (p = 0.01), and concerns during the index attack about taking time off work (p = 0.07)--the model being responsible for 21% of the variance., Conclusions: The results of this study show that, despite recent educational advances, serious management errors are common in those admitted to hospital with acute severe asthma and that most management errors relate to patient self-management behaviour. Serious management errors are predicted by a variety of socio-economic and psychological factors. While the results of this study are consistent with the widely held view that most acute severe attacks are theoretically preventable, the challenge for the future is to change patients' behaviour in the face of considerable adverse socioeconomic and psychological factors.

Background: A study was undertaken to test the hypothesis that a particular inhaled beta agonist, fenoterol, increases the incidence of severe life threatening asthma., Methods: A retrospective cohort was assembled comprising 655 patients with asthma aged 15-55 years who attended a single Auckland hospital for acute asthma between 1 January 1986 and 31 December 1987 (the "index event"). Patients were followed for the occurrence of death from asthma or admission to the intensive care unit for asthma, until death or 31 May 1989. Data on asthma medications and asthma severity were obtained from forms used specifically for managing patients with acute asthma in the emergency department and maintained as part of the hospital record and/or from the hospital record (when patients were admitted)., Results: Following the index event 90 admissions to the intensive care unit (ICU) and 15 asthma deaths were identified. Before adjusting for asthma severity, patients using inhaled fenoterol had a greater incidence of severe life threatening asthma than patients using inhaled salbutamol (RR = 2.1, 95% CI 1.4 to 3.1). After controlling for two markers of severe asthma used in previous studies-a hospital admission in the previous year and prescribed oral corticosteroids-the relative risk estimate declined to 1.5 (95% CI 1.0 to 2.3). After controlling further for the number of hospital admissions during the study period, continuous oral corticosteroid use rather than short courses of treatment, severity of the previous attack requiring a hospital visit, and race, fenoterol was not associated with severe life threatening asthma at the time of attendance for a previous hospital visit (RR = 1.0, 95% CI 0.6 to 1.7)., Conclusion: Fenoterol is used more often by patients with severe asthma and, after adjusting for differences in baseline risk, it does not increase the risk of severe life threatening asthma.

Increasing financial barriers to primary health care against a background of social and economic decline are likely to have contributed to asthma morbidity and mortality in New Zealand. Although there would not have been a sufficient increase in asthma prevalence to have accounted for the threefold increase in mortality rates, whether or not there was an increase in asthma severity in the late 1970s remains open to debate. Misuse or poor use of newly available and potent bronchodilator medications by those with the most severe asthma may simply have contributed to further delays in obtaining appropriate care and therefore to an increase in frequency of severe attacks in the community. Despite substantial increases in the use of bronchodilator therapy in New Zealand, there was no immediate improvement in indices of either asthma morbidity or mortality. The initial reduction in mortality rates in the 1980s happened at a time when first admissions for asthma were still increasing and seems to be best explained by an improvement in utilisation of hospital services (which were free until 1992) rather than a reduction in asthma severity. However, the recent reductions in all measures of asthma morbidity and further reduction in asthma mortality since 1989 does now suggest a reduction in asthma severity and would be best explained by the substantial increase in medium and high dose inhaled corticosteroid use, and to the endorsement of the current management strategies for asthma which are being promoted internationally and which were given considerable publicity in New Zealand in 1989 and 1990. Whilst sales of inhaled beta agonists were higher in 1991 than 1989, this may not reflect their pattern of use by individual patients since the need for an increase in inhaled beta agonist treatment has been accepted as indicating a lack of control and the need for either starting or increasing the dose of inhaled steroid treatment.

Background: Studies of mortality from asthma have suggested that a very severe asthma attack identifies a group at greatly increased risk of subsequent death from the disease. This study compares the demographic characteristics of asthmatic patients who required management in an intensive care unit for a severe life threatening attack between 1981 and 1987 with a group who died of asthma between 1980 and 1986. The outcome of the group admitted to an intensive care unit is described., Methods: The groups comprised all cases aged between 15 and 49 years arising from the Auckland Area Health Board (AAHB) population who required admission to an intensive care unit for asthma between 1981 and 1987 (n = 413) and all deaths from asthma in those aged 15 to 49 years arising from the New Zealand population between 1980 and 1986 (n = 466). Details of age, sex, and information on the day and month of the attack were collected. For the group requiring admission to an intensive care unit, outcome in terms of mortality and readmission to intensive care was determined., Results: The age distributions of the two groups were dissimilar, with the severe life threatening attack group having an excess of asthmatic patients under 30 years old. The distribution of events by calendar month was uniform in both groups, but there was an unexpected increase in frequency of attacks on Sundays in both groups. Over the study period, mortality fell from 5.3 per 100,000 to 3.5 per 100,000 but the admission rate to intensive care increased from 10.8 per 100,000 to 17.9 per 100,000. At least 24% of asthma deaths occurring in the AAHB region during the study period had previously experienced a severe life threatening attack., Conclusions: The similarities between the groups suggest that asthmatic patients who experience severe life threatening attacks are likely to come from the same subgroup of the asthma population as those who die. The group who experience severe life threatening attacks are at high risk of subsequent morbidity and mortality and further studies may produce information relevant to reducing mortality from asthma.