VEGFR-2, CXCR-2 and PAR-1 germline polymorphisms as predictors of survival in pancreatic carcinoma.

BACKGROUND: Hypoxic environment of pancreatic cancer (PC) implicates high vascular in-growth, which may be influenced by angiogenesis-related germline polymorphisms. Our purpose was to evaluate polymorphisms of vascular endothelial growth factor receptor 2 (VEGFR-2), CXC chemokine receptor 2 (CXCR-2), proteinase-activated receptor 1 (PAR-1) and endostatin (ES) as prognostic markers for disease-free (DFS) and overall survival (OS) in PC. PATIENTS AND METHODS: Genotyping of 173 patients, surgically treated for PC between 2004 and 2011, was carried out by TaqMan(®) genotyping assays or polymerase chain reaction. Chi-square test, Kaplan-Meier estimator and Cox regression hazard model were used to assess the prognostic value of selected polymorphisms. RESULTS: VEGFR-2 -906 T/T and PAR-1 -506 Del/Del genotypes predicted longer DFS (P = 0.003, P = 0.014) and OS (VEGFR-2 -906, P = 0.011). CXCR-2 +1208 T/T genotype was a negative predictor for DFS (P < 0.0001). Combined analysis for DFS and OS indicated that patients with the fewest number of favorable genotypes simultaneously present (VEGFR-2 -906 T/T, CXCR-2 +1208 C/T or C/C and PAR-1 -506 Del/Del) were at the highest risk for recurrence or death (P < 0.0001). CONCLUSION: VEGFR-2 -906 C>T, CXCR-2 +1208 C>T and PAR-1 -506 Ins/Del polymorphisms are potential predictors for survival in PC.

Comparison of recommendations for radiotherapy from two contemporaneous thoracic multidisciplinary meeting formats: co-located and video conference.

BACKGROUND: Thoracic multidisciplinary meetings (TMDM) are a key component of lung cancer patient management. The optimal design, organisation and function of TMDM are uncertain, and different models may serve different purposes. In the Auckland/Northland region, there are two contemporaneous weekly TMDM using different formats; one is a co-located TMDM (C-TMDM), and the other is a video conference TMDM (V-TMDM) connecting different locations. AIMS: To determine whether the rates of referral for radiotherapy (RT) and concordance between recommendations for RT and actual treatment received differed between the two TMDM formats. METHOD: A retrospective review of demographical and clinical data for cases referred for RT from both TMDM between January-June 2009 and the actual RT delivered. RESULTS: Seventy-nine and 31 lung cancers were referred for RT from the co-located TMDM and the video conference TMDM respectively. While there were significant differences in demographics related to areas of domicile, there were no significant differences between the TMDM in (i) the proportion of cases referred for RT that received RT, (ii) the intent of treatment recommended by the TMDM and the intent of RT delivered, or (iii) transit times to commencement of RT between cases referred from the different TMDM. CONCLUSION: The similar results from the different formats of TMDM indicate that cases discussed with the use of e-health technologies are not disadvantaged with respect to recommended therapy nor in the appropriateness of decisions of the TMDM. Use of such technology may reduce the existing disparities in health outcomes between urban and rural patients.

Inhaled dry powder mannitol in cystic fibrosis: an efficacy and safety study.

This international phase III study of inhaled dry powder mannitol was a randomised, double-blind, 26-week study, followed by a further 26-week, open-label (OL) extension. 324 cystic fibrosis (CF) patients were randomised, in a 3:2 ratio, to mannitol (400 mg b.i.d.) and control groups. The primary efficacy end-point was to determine the change in forced expiratory volume in 1 s (FEV1) over the double-blind phase. Secondary end-points included changes in forced vital capacity and pulmonary exacerbations. A significant improvement in FEV1 was seen over 26 weeks (p<0.001) and was apparent by 6 weeks, irrespective of concomitant recombinant human deoxyribonuclease (rhDNase) use. At 26 weeks, there was a significant improvement in FEV1 of 92.9 mL for subjects receiving mannitol compared with controls (change from baseline 118.9 mL (6.5%) versus 26.0 mL (2.4%); p<0.001). Improvements in FEV1 were maintained up to 52 weeks in the OL part of the study. There was a 35.4% reduction in the incidence of having an exacerbation on mannitol (p=0.045). The incidence of adverse events (AEs) was similar in both groups, although treatment-related AEs were higher in the mannitol compared with the control group. The most common mannitol-related AEs were cough, haemoptysis and pharyngolaryngeal pain. Mannitol showed sustained, clinically meaningful benefit in airway function in CF, irrespective of concomitant rhDNase use. Mannitol appears to have an acceptable safety profile for patients with CF.

Isolated nocturnal desaturation in COPD: prevalence and impact on quality of life and sleep.

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.

Pseudomonas aeruginosa transmission is infrequent in New Zealand cystic fibrosis clinics.

Pseudomonas aeruginosa is an important pathogen in cystic fibrosis (CF). Although most patients harbour unique P. aeruginosa isolates, some clinics report patients sharing common strains. The overall importance of person-to-person transmission in P. aeruginosa acquisition and whether routine patient segregation is necessary remains uncertain. The present authors therefore investigated the extent of P. aeruginosa transmission in New Zealand CF clinics. New Zealand's seven major CF centres were assessed, combining epidemiological data with computer-assisted SalI DNA fingerprinting of 496 isolates from 102 patients. One cluster of related isolates was significantly more prevalent in the largest clinic than expected by chance. The seven patients with isolates belonging to this cluster had more contact with each other than the remaining patients attending this centre. No other convincing evidence of transmission was found in any of the other smaller clinics. Three P. aeruginosa strains believed to be transmissible between patients in Australian and British CF clinics are present in New Zealand, but there was no definite evidence they had spread. Pseudomonas aeruginosa transmission is currently infrequent in New Zealand cystic fibrosis clinics. This situation could change rapidly and ongoing surveillance is required. The current results confirm that computer-assisted SalI DNA fingerprinting is ideally suited for such surveillance.

Management of stages I and II non-small-cell lung cancer in a New Zealand study: divergence from international practice and recommendations.

BACKGROUND: Lung cancer survival statistics for New Zealand (NZ) are poor relative to Australia, USA, Canada and some European countries for reasons that are unknown. As patients with early-stage non-small-cell lung cancer (NSCLC) have the highest chance of survival, appropriate management disproportionately influences survival rates. The aim of this study was to assess management of stage I/II NSCLC, whether management differed from international practice, and factors influencing curative management. METHODS: Management of patients with stages I and II NSCLC was determined from an audit of secondary care in Auckland and Northland for patients with lung cancer diagnosed in 2004 (565). RESULTS: Of the 142 cases with stage I or II NSCLC, 79 patients (56%) were treated with curative intent and 61 (44%) were managed palliatively. Of those treated curatively, 69 underwent surgical resection, 9 received definitive radiation therapy and a single patient received concurrent chemo-irradiation. Of those managed palliatively, 21 received anticancer treatment and 40 received supportive care. Increasing age and comorbidity reduced the chances of receiving curative treatment (P < 0.001, P = 0.004, respectively); however, discussion at a multidisciplinary meeting was associated with increased likelihood of curative management (P < 0.001). Disparity between NZ and overseas practice increased with increasing age and comorbidity. Only half of those managed curatively commenced treatment within internationally recommended time frames. CONCLUSION: Relatively fewer patients received potentially curative treatment in this NZ study than in countries with better survival outcomes and many were not managed within recommended time frames. Management differences increased with increasing age and comorbidity, possibly suggesting more nihilistic attitudes in NZ.

A randomized evaluation of the acute efficacy, acceptability and tolerability of flutter and active cycle of breathing with and without postural drainage in non-cystic fibrosis bronchiectasis.

Airway clearance is integral to the management of bronchiectasis, yet there is no evidence as to the optimal modality. The aim of this randomized prospective study was to evaluate the acute efficacy, acceptability and tolerability of three airway clearance techniques in non-cystic fibrosis (non-CF) bronchiectasis. Flutter, active cycle of breathing technique (ACBT) and ACBT with postural drainage (ACBT-PD) were evaluated in random order over a week in 36 patients (mean age 62 years, range 33-83), with stable non-CF bronchiectasis. Total sputum wet weight for ACBT-PD was twice that of either ACBT alone or Flutter. No objective difference in treatment duration was noted. All three techniques were well accepted and tolerated. Patient preference was 16 (44%) for Flutter, eight (22%) ACBT and 12 (33%) for ACBT-PD. Patient demography, factors such as upper airways or reflux symptoms, previous use or acute efficacy did not predict preference. This is the first randomized systematic evaluation of acute efficacy, acceptability and tolerability of Flutter, ACBT and ACBT-PD in non-CF bronchiectasis. All three techniques were well tolerated but ACBT-PD proved superior in terms of acute efficacy. Patient preference for treatment modality could not be predicted.

Overnight prescription of oxygen in long term oxygen therapy: time to reconsider the guidelines?

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.

Short-burst oxygen therapy for COPD patients: a 6-month randomised, controlled study.

Short-burst oxygen therapy (SBOT) remains widely advocated for patients with chronic obstructive pulmonary disease (COPD), despite a lack of supporting evidence. The aim of this randomised, double-blind, placebo-controlled, parallel group study was to determine whether SBOT improves health-related quality of life (HRQL) or reduces acute healthcare utilisation in patients discharged following an acute exacerbation of COPD. Consecutive patients were screened; 78 of 331 were eligible for randomisation to cylinder oxygen, cylinder air or usual care following discharge. Patients were elderly with high acute healthcare utilisation, forced expiratory volume in one second of <1 L and had dyspnoea limiting daily activity but were not hypoxaemic at rest. Over the 6-month study period, there were no significant differences between patient groups in HRQL (Chronic Respiratory Questionnaire (CRQ), 36-item Short-Form Health Survey, Hospital Anxiety and Depression Scale) except for CRQ emotion domain. There were no significant differences in acute healthcare utilisation. Time to readmission was greatest in the usual care group. Cylinder use was high initially, but rapidly fell to very low levels within weeks in both cylinder oxygen and air groups. In conclusion, the availability of short-burst oxygen therapy for chronic obstructive pulmonary disease patients discharged from hospital following an acute exacerbation did not improve health-related quality of life or reduce acute healthcare utilisation. These results provide no support for the widespread use of short-burst oxygen therapy.

The endurance shuttle walking test: a responsive measure in pulmonary rehabilitation for COPD patients.

BACKGROUND: The endurance shuttle walk test (ESWT) is a standardized externally controlled constant paced field test for the assessment of endurance capacity in chronic lung disease. The ESWT has been advocated as a simple, acceptable, repeatable and responsive outcome measure for COPD patients undergoing pulmonary rehabilitation, but has not been formally compared with the more commonly used field walking test, the six-minute walk (6MW). We aimed to determine: 1) the responsiveness of the ESWT in COPD patients attending a hospital-based pulmonary rehabilitation programme, and 2) to compare the responsiveness of the ESWT with the 6MW. METHODS: Consecutive COPD patients, referred for a standard 8 week pulmonary rehabilitation programme, were recruited. Outcome parameters studied at baseline and completion of rehabilitation programme (8 weeks) included spirometric lung volumes, resting oxygen saturation, breathlessness scored pre and post exercise (modified Borg dyspnoea score), 6MW, ESWT, health-related quality of life (Chronic Respiratory Questionnaire) and Hospital Anxiety and Depression (HAD) scale. The incremental shuttle was employed to predict VO2 peak; 85% VO2 peak was used to determine the walk speed for the ESWT. RESULTS: Twenty stable COPD patients (11 male), mean (SD), age 71, (9) FEV1 0.95 (0.51), resting SpO2 95% (2) 6MW distance (m) 351 (104) and ESWT distance (m) 313 (193) were studied. Three patients did not complete their rehabilitation programme. Following rehabilitation, there were significant improvements in 6MW, ESWT, total CRQ and anxiety domain (HAD). The 6MW distance increased by 17% (47 m 95%CI 3, 90), while the ESWT increased by 92% (302 m 95%CI 104, 501). CONCLUSION: The ESWT is a simple, acceptable and highly responsive outcome measure for COPD patients undergoing a pulmonary rehabilitation programme. The ESWT has potential advantages in that it may be more responsive than the 6MW.

The Dartmouth COOP Charts: a simple, reliable, valid and responsive quality of life tool for chronic obstructive pulmonary disease.

The negative impact of chronic obstructive pulmonary disease (COPD) on health-related quality of life (HRQL) is substantial. Measurement of HRQL is increasingly advocated in clinical practice; traditional outcome measures such as lung function are poorly responsive. However many HRQL tools are not user-friendly in the clinic setting. Hence HRQL is often neglected. The Dartmouth Cooperative Functional Assessment Charts (COOP) have the requisite attributes of a tool suitable for routine clinical practice: they are simple, reliable, quick and easy to perform and score and well accepted. We aimed to determine the reliability, validity and responsiveness of the COOP in patients with significant COPD. HRQL was assessed during a prospective, randomised, placebo-controlled, double-blind, 12 week cross-over interventional study of ambulatory oxygen in patients (n = 50) with COPD. Test-retest reliability of the COOP domains was only modest however it was measured over a 2 month period. Significant correlations ranging between 0.4 and 0.8 were observed between all comparable domains of the COOP and the Medical Outcomes Study 36-item Short-form Health Survey, Chronic Respiratory Questionnaire (CRQ) and Hospital Anxiety and Depression (HAD) scale. Following ambulatory oxygen significant improvements were noted in all CRQ and HAD domains. Several domains of the generic SF-36 (role emotional, social functioning, role-physical) showed significant improvements. Comparable domains of the COOP (social activities, feelings) also showed significant improvements. The COOP change in health domain improved very significantly. The COOP is a simple, reliable HRQL tool which proved valid and responsive in our study population of COPD patients and may have a valuable role in routine clinical practice.

Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children.

New Zealand children's morbidity from respiratory disease is high. This study examines whether subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. A prospective study enrolled a group of healthy children who were screened for respiratory disease by questionnaire and lung function. Skin-prick tests were performed to control for atopy. Exhaled and nasal NO was measured online by a single-breath technique using chemiluminescence. Ciliary specimens were obtained by nasal brushings for assessment of structure and function. The ciliary beat frequency (CBF) (median CBF, 12.5 Hz; range, 10.4-16.8 Hz) and NO values (median exhaled NO, 5.6 ppb; range, 2.3-87.7 ppb; median nasal NO, 403 ppb; range, 34-1,120 ppb) for healthy New Zealand European (n=58), Pacific Island (n=61), and Maori (n=16) children were comparable with levels reported internationally. No ethnic differences in NO, atopy, or CBF were demonstrated. Despite an apparently normal ciliary beat, the percentage of ciliary structural defects was 3 times higher than reported controls (9%; range, 3.6-31.3%), with no difference across ethnic groups. In conclusion, it is unlikely that subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. The high percentage of secondary ciliary defects suggests ongoing environmental or infective damage.

Long-term oxygen therapy improves health-related quality of life.

Guidelines for the prescription of long-term oxygen therapy (LTOT) in hypoxemic COPD patients are based on two landmark studies in which survival was the primary outcome. Such patients are importantly symptomatic with poor health-related quality of life (HRQL) but the effect of LTOT on HRQL remains uncertain. We undertook a prospective longitudinal interventional study of consecutive COPD patients referred to our regional oxygen service; n = 43 fulfilling criteria and commenced on LTOT, n = 25 not fulfilling criteria and continued on standard care. HRQL was measured at baseline, 2 and 6 months. Both patient groups had severe COPD as defined by mean FEV1 < 35% predicted. At baseline the LTOT group demonstrated significantly worse HRQL as defined by the Chronic Respiratory Questionnaire (CRQ) (fatigue, emotional function, mastery and total scores), total generic Dartmouth COOP Charts and anxiety domain of the Hospital Anxiety and Depression scale. Significant improvements in HRQL were noted at 2 and 6 months in the LTOT group. Conversely the non-LTOT group demonstrated a progressive decline in HRQL. Using validated criteria for a minimal clinically significant improvement in CRQ, there were 28 (67%) and 26 (68%) 'responders' at 2 and 6 months respectively in the LTOT group. The introduction of LTOT to patients with severe COPD fulfilling standard criteria was associated with early significant improvements in HRQL with sustained or further response at 6 months.

Increased risk of adverse events when changing intravenous immunoglobulin preparations.

Intravenous immunoglobulin (IVIG) therapy has represented a major advance in the treatment of patients with primary immune deficiency disorders. In September 2000 a new IVIG formulation, Intragam P, was introduced into clinical use. Intragam P is prepared by delipidation of pooled plasma followed by an ion exchange chromatography step to eliminate immunoglobulin aggregates. It is then pasteurized for 10 h at 60 degrees C for viral inactivation before storage at pH 4.25 in 10% maltose. We report initial clinical experience with this new preparation. The details of adverse reactions of patients who received the new preparation were gathered shortly after it became apparent there was a change in IVIG formulation. Seven of 49 patients receiving Intragam P spontaneously reported adverse effects, which were temporally related to infusions. Subsequently, all seven patients have been able to tolerate the product with prophylactic use of antihistamines and paracetamol. This case series indicates that long-term tolerance of an older IVIG product does not necessarily equate to tolerance to a newer product, even if technically superior. Caution should be exercised when changing IVIG products, as they are not biologically equivalent.

Short-burst oxygen immediately before and after exercise is ineffective in nonhypoxic COPD patients.

Short-burst oxygen therapy (SBOT) remains an unproven treatment for reduction of exertional dyspnoea in chronic obstructive pulmonary disease (COPD). This study aimed to assess whether SBOT before exercise reduces dyspnoea or improves performance, and whether SBOT after exercise reduces dyspnoea during recovery. Twenty-two clinically stable COPD patients (mean forced expiratory volume in one second 34% predicted, mean resting saturation 94%) attended a respiratory gymnasium and undertook four 6-min walk (6MW) tests at each of two sessions, 1 week apart. Cylinder air or oxygen was administered single-blind in random order for 5 min prior to the first two 6MW and during recovery following the final two 6MW. Dyspnoea was self-rated by subjects using the modified Borg scale. There was no significant difference in mean 6MW distance or final Borg score for air and oxygen given before exercise. There was also no significant difference in mean time-to-resting Borg score for air and oxygen given after exercise. Only two subjects demonstrated a clinically significant and consistent reduction in dyspnoea for oxygen compared with air either before or after exercise. Overall, short-burst oxygen therapy neither reduced dyspnoea nor improved performance. This study does not support the use of short-burst oxygen therapy either immediately before or after exercise.

Ambulatory oxygen improves quality of life of COPD patients: a randomised controlled study.

It is unknown whether acute response to ambulatory oxygen (O2) predicts longer term improvement in health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) patients. The aims of this study were 1) to assess the short-term clinical impact, as determined by HRQL, of ambulatory O2 in a 12-week, double-blind, randomised crossover study of O2 (versus cylinder compressed air) of dyspnoeic but not chronically hypoxic COPD patients with exertional desaturation < or = 88% (n=41), and 2) to determine whether either baseline characteristics or acute response to O2 predicts short-term (12 weeks) response. Primary outcome measures were Chronic Respiratory Questionnaire (CRQ), Hospital Anxiety and Depression scale and the short form (SF)-36. Improvements were seen in all domains of the CRQ for cylinder O2 compared with cylinder air. Significant improvements were also noted in anxiety and depression and in certain domains of the SF-36. There were 28 (68%) acute responders to cylinder O2 (defined as increase in 6-min walk > or = 54 m or decrease in post-Borg dyspnoea > or = 1) and 23 (56%) short-term responders (defined as clinically significant improvement in CRQ). However, acute and short-term responses were not correlated with no predictors of short-term response identified. At study completion, 14 (41%) of acute or short-term responders did not want to continue therapy, with 11 citing poor acceptability or tolerability. Short-term ambulatory oxygen is associated with significant improvements in health-related quality of life. These benefits cannot be predicted by baseline characteristics or acute response. Despite acute or short-term response, a substantial proportion of patients declined ambulatory oxygen.

Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions?

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.

Case-control study of severe life threatening asthma (SLTA) in adults: psychological factors.

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.

Spirometric lung volumes in the adult Pacific Islander population: comparison with predicted values in a European population.

OBJECTIVE: Prediction equations for spirometric lung volumes have been developed mainly in Europe and North America and may not be relevant to Pacific Islanders. This study was undertaken to determine whether currently available prediction equations adequately describe spirometric lung volumes in the asymptomatic adult Pacific Islander population. METHODOLOGY: Healthy asymptomatic Pacific Island adults aged 15-70 years were recruited. Pulmonary function was measured in the laboratory at Green Lane Hospital, Auckland, New Zealand, in accordance with American Thoracic Society standards. Measured results were compared with predicted values derived from four sets of prediction equations relevant to, or currently used in, New Zealand. RESULTS: A total of 101 volunteers took part in the study; mean age 28 years (range 18-66 years), 39% male, body mass index = 32 (range 22-54). For forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), when measured values were compared with reference values, the slopes of the regression lines were not significantly different from 1 and the intercepts were not significantly different from zero. Prediction equations derived for African-Americans did not provide a better fit than the prediction equations for Caucasians. Predictions were improved when ideal rather than actual bodyweight was used. CONCLUSION: Respiratory parameters (FEV1 and FVC) in healthy asymptomatic adult Pacific Islanders in New Zealand are adequately described by currently available prediction equations and no adjustment for ethnicity is required.