In patients with unilateral pleural effusion, restricted lung inflation is the principal predictor of increased dyspnoea.

BACKGROUND AND OBJECTIVE: The mechanism of dyspnoea associated with pleural effusion is uncertain. A cohort of patients requiring thoracoscopy for unilateral exudative effusion were investigated for associations between dyspnoea and suggested predictors: impaired ipsilateral diaphragm movement, effusion volume and restricted lung inflation. METHODS: Baseline Dyspnoea Index, respiratory function, and ultrasound assessment of ipsilateral diaphragm movement were assessed prior to thoracoscopy, when effusion volume was measured. Transitional Dyspnoea Index (change from baseline) was assessed 4 and 8 weeks after thoracoscopy. Pearson product moment assessed bivariate correlations and a general linear model examined how well total lung capacity (measuring restricted lung inflation), effusion volume and impaired diaphragm movement predicted Baseline Dyspnoea Index. Un-paired t tests compared the groups with normal and impaired diaphragm movement. RESULTS: 19 patients were studied (14 malignant etiology). Total lung capacity was associated with Baseline Dyspnoea Index (r = 0.68, P = 0.003). Effusion volume (r = -0.138, P = 0.60) and diaphragm movement (P = 0.09) were not associated with Baseline Dyspnoea Index. Effusion volume was larger with impaired diaphragm movement compared to normal diaphragm movement (2.16 ±SD 0.95 vs.1.16 ±0.92 L, P = 0.009). Total lung capacity was lower with impaired diaphragm movement compared to normal diaphragm movement (65.4 ±10.3 vs 78.2 ±8.6% predicted, P = 0.011). The optimal general linear model to predict Baseline Dyspnoea Index used total lung capacity alone (adjusted R2 = 0.42, P = 0.003). In nine participants with controlled effusion, baseline effusion volume (r = 0.775, P = 0.014) and total lung capacity (r = -0.690, P = 0.040) were associated with Transitional Dyspnoea Index. CONCLUSIONS: Restricted lung inflation was the principal predictor of increased dyspnoea prior to thoracoscopic drainage of effusion, with no independent additional association with either effusion volume or impaired ipsilateral diaphragm movement. Restricted lung inflation may be an important determinant of the dyspnoea associated with pleural effusion.

Screen-detected subsolid pulmonary nodules: long-term follow-up and application of the PanCan lung cancer risk prediction model.

OBJECTIVE: To report the long-term follow-up of subsolid nodules (SSNs) detected in participants of a prospective low-dose CT lung cancer screening cohort, and to investigate the utility of the PanCan model in stratifying risk in baseline SSNs. METHODS: Participants underwent a baseline scan, two annual incidence scans and further follow-up scans for the detected nodules. All SSNs underwent a minimum of 2 years of follow-up (unless resolved or resected). Risk of malignancy was estimated using the PanCan model; discrimination [area under the receiver-operating characteristic curve (AUC)] and calibration (Hosmer-Lemeshow goodness-of-fit test) were assessed. The Mann-Whitney U-Wilcoxon test was used to compare estimated risk between groups. RESULTS: 70 SSNs were detected in 41 (16.0%) out of 256 total participants. Median follow-up period was 25.5 months (range 2.0-74.0 months). 29 (41.4%) SSNs were transient. Five (7.1%) SSNs were resected, all found to be Stage I lung adenocarcinoma, including one SSN stable in size for 3.0 years before growth was detected. The PanCan model had good discrimination for the 52 baseline SSNs (AUC = 0.89; 95% confidence interval 0.76-1); the Hosmer-Lemeshow goodness-of-fit test was non-significant (p = 0.27). Estimated risk was significantly higher in the baseline SSNs found to be cancer vs those not found to be cancer after 2-6 years of follow-up (p < 0.01). CONCLUSION: Our findings support a long-term follow-up approach for screen-detected SSNs for 3 years or longer. The PanCan model appeared discriminatory and well calibrated in this cohort. ADVANCES IN KNOWLEDGE: The PanCan model may have utility in identifying low-risk SSNs which could be followed with less frequent CT scans.

Exhaled breath analysis for lung cancer.

Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection.

Genetic influences on right ventricular systolic pressure (RVSP) in chronic obstructive pulmonary disease (COPD).

BACKGROUND: Pulmonary hypertension (PH) is a complication of chronic obstructive pulmonary disease (COPD). This study examined genetic variations in mediators of vascular remodelling and their association with PH in patients with COPD. In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. METHODS: In patients with COPD, we genotyped 7 SNPs in 6 candidate PH genes (NOS3, ACE, EDN1, PTGIS, SLC6A4, VEGFA). We tested for association with right ventricular systolic pressure (RVSP), spirometry and gas transfer, and hypoxemia. RESULTS: 580 COPD patients were recruited, 341 patients had a transthoracic echocardiogram, with RVSP measurable in 278 patients (mean age 69 years, mean FEV1 50% predicted, mean RVSP 44 mmHg, median history of 50 pack-years). Of the 7 tested SNPs, the NOS3-VNTR polymorphism was significantly associated with RVSP in a dose-dependent fashion for the risk allele: mean RVSP for a/a and a/b genotypes were 52.0 and 46.6 mmHg respectively, compared to 43.2 mmHg for b/b genotypes (P = 0.032). No associations were found between RVSP and other polymorphisms. ACE II or ID genotypes were associated with a lower FEV1% predicted than the ACE DD genotype (P = 0.028). The NOS3-298 TT genotype was associated with lower KCO % predicted than the NOS3-298 GG or GT genotype (P = 0.031). CONCLUSIONS: The NOS3-VNTR polymorphism was associated with RVSP in patients with COPD, supporting its involvement in the pathogenesis of PH in COPD. ACE and NOS3 genotypes were associated with COPD disease severity, but not with the presence of PH. Further study of these genes could lead to the development of prognostic and screening tools for PH in COPD.

Variability in the rate of prescription and cost of domiciliary oxygen therapy in Australia.

OBJECTIVES: To determine the rate of prescription of and government expenditure for domiciliary oxygen therapy (DOT) in Australia, and to identify interstate differences in rates, costs and service provision. DESIGN: Retrospective observational study. PARTICIPANTS AND SETTING: Government departments and health services (state and federal) that funded DOT in Australia in the 2004-05 financial year (including the Department of Veterans' Affairs [DVA] and the Department of Health and Ageing [DoHA]). MAIN OUTCOME MEASURES: Prescription rates, cost of DOT in 2004-05, and services provided in each jurisdiction. RESULTS: In 2005, 20,127 patients were using DOT, giving a national prevalence of 100 prescriptions per 100,000 population. The total cost was about $31 million. State governments, the DVA and the DoHA funded 13,899 (69%), 4084 (20%) and 2144 (11%) patients, respectively. Prescription rates varied threefold between the states, ranging from 44 (Northern Territory) to 133 (Tasmania) per 100,000 population. Cost per patient per year varied fourfold between the DVA and the DoHA. All jurisdictions funded oxygen according to the clinical criteria of the Thoracic Society of Australia and New Zealand, but considerable variability in service provision was identified. CONCLUSION: DOT prescription rates and costs vary considerably between jurisdictions. An urgently needed national DOT register would enable the current variability to be understood and allow service planning and benchmarking of clinical outcomes.

Quantified tracheobronchomalacia disorders and their clinical profiles in children.

BACKGROUND: Tracheobronchomalacia (TBM) disorders in children have never been studied using quantified measurements and validated clinical outcome measures. The objectives of the study were to prospectively examine the relationship between malacia lesions and their respiratory illness profiles. METHODS: The site of malacia lesions (eg, tracheomalacia, TBM, and bronchomalacia) were determined, measured, and related to the respective cricoid (ie, airway/cricoid ratio) using the color histogram mode technique. These children and normal control subjects were followed up for 12 months with their respiratory illness profiles determined using the Canadian Acute Respiratory Illness Scale (CARIFS) and cough diary scores. MEASUREMENTS: Outcome measures were respiratory illness frequency (> 12 months), severity score (day-1 CARIFS score), and significant cough interfering with daily activity (score of >or= 3) and illness resolution (time to return to a quarter of CARIFS day 1 score). RESULTS: The group of 116 children were composed of patients with malacia (n = 81) and control subjects (n = 35). The median age of the group was 2.1 years (age range, 0.2 to 17.3 years). The adjusted relative risk of illness frequency was 2.1 (95% confidence interval [CI], 1.3 to 3.4), and of significant cough was 7.2 (95% CI, 1.01 to 27.22) for the malacia group while CARIFS day 1 score was 1.66 (95% CI, 1.1 to 2.56) compared to control subjects. Illness resolution rates at day 14 in the malacia group trended 25% slower than those for control subjects. Malacia type and severity of lesions were not associated with increased rates of illness or worse clinical profiles. CONCLUSION: Children with malacia have an increased likelihood of respiratory illness frequency, severity, significant cough, and tendency for delayed recovery. However, neither the site nor the severity of malacia exhibited any significant dose effect on respiratory illness profiles.

Longitudinal quantification of growth and changes in primary tracheobronchomalacia sites in children.

RATIONALE: Longitudinal follow-up of children with tracheobronchomalacia is essential to improving our understanding of these disorders, yet currently, there is no such data. OBJECTIVES: To longitudinally define malacia sites and quantify the cross-sectional area (CSA) of the lumen using a bronchoscopic technique and to relate these measurements to illness profiles. METHODS: The validated color histogram mode technique was utilized to quantify primary malacia lesions and airway sites' CSA. Illness frequency, validated scales of illness and cough diary scores were prospectively used to assess clinical profiles. RESULTS: Thirty-five malacia sites were defined from the 2 studies of 21 children. CSA of 21 (60%) of the malacia lesions increased, 5 (14%) new lesions appeared, 5 (14%) decreased in size, 3 (8%) remained unchanged, and 1(3%) was indeterminate. Overall there was no statistically significant change in paired-data assessments of malacia sites' area while there was a significant increase in area of non-malacia sites. The median yearly growth rate for the malacia sites and non-malacia was 3.65 mm2/year sites and 5.38 mm2/year, respectively (P = 0.31). The type and severity of lesion was not associated with any difference in growth rates, illness frequency or clinical scores. CONCLUSIONS: Malacia lesions increase in size at the same rate as non-malacia sites. However malacia may worsen and new primary lesions may develop. Neither malacia type nor severity influences their growth pattern or illness profile.

Airway sizes and proportions in children quantified by a video-bronchoscopic technique.

BACKGROUND: A quantitative understanding of airway sizes and proportions and a reference point for comparisons are important to a pediatric bronchoscopist. The aims of this study were to measure large airway areas, and define proportions and factors that influence airway size in children. METHODS: A validated videobronchoscope technique was used to measure in-vivo airway cross-sectional areas (cricoid, right (RMS) and left (LMS) main stem and major lobar bronchi) of 125 children. Airway proportions were calculated as ratios of airways to cricoid areas and to endotracheal tube (ETT) areas. Mann Whitney U, T-tests, and one-way ANOVA were used for comparisons and standard univariate and backwards, stepwise multivariate regression analyses were used to define factors that influence airway size. RESULTS: Airways size increased progressively with increasing age but proportions remained constant. The LMS was 21% smaller than the RMS. Gender differences in airways' size were not significant in any age group or airway site. Cricoid area related best to body length (BL): cricoid area (mm2) = 26.782 + 0.254* BL (cm) while the RMS and LMS area related best to weight: RMS area (mm2) = 23.938 + 0.394*Wt (kg) and LMS area (mm2) = 20.055 + 0.263*Wt (kg) respectively. Airways to cricoid ratios were larger than airway to ETT ratios (p = 0.0001). CONCLUSION: The large airways progressively increase in cross sectional area size, maintain constant proportional relationships to the cricoid and are gender independent across childhood. Anthropometric factors (body length and weight) are significantly related to but only have weakly predictive influences on major airway size. The cricoid is the most suitable comparator for other airway site measurements. These data provide for quantitative comparisons of airway lesions.

Effectiveness of hospital-based smoking cessation.

STUDY OBJECTIVES: Smoking cessation for current smokers is a health-care imperative. It is not clear which approaches to smoking cessation are the most effective in the hospital setting and which factors predict long-term abstinence. We hypothesized that a hospital-based smoking cessation program involving behavioral modification and support would provide an effective intervention for smoking cessation. DESIGN: Prospective cohort study. SETTING: Smoking cessation clinics in a tertiary referral, cardiothoracic hospital. PATIENTS OR PARTICIPANTS: Two hundred forty-three smokers and 187 never-smoker control subjects. INTERVENTIONS: Smokers underwent specific sessions of individual counseling on behavioral modification, including written information, advice about quit aids, and support during the quit attempt. Abstinence was confirmed by exhaled carbon monoxide measurements. MEASUREMENTS AND RESULTS: Compared to never-smoker control subjects, smokers were more likely to have grown up with a smoking father or siblings, and to currently live or socialize with other smokers. Two hundred sixteen smokers attended at least two sessions of the smoking cessation program. Of these, 25% were unavailable for follow-up at 12 months and were assumed to be smoking. The point prevalence abstinence rate at 12 months was 32%. Independent factors associated with abstinence at 12 months were self-belief in quitting ability, having a heart condition, growing up without siblings who smoked, and increasing number of pack-years. CONCLUSIONS: This prospective study has demonstrated that this hospital-based smoking cessation program was as effective as programs in other settings. Social and psychological factors were associated with a greater chance of abstinence.

Transient elevation of the tumor markers CA 15-3 and CASA as markers of interstitial lung disease rather than underlying malignancy in dermatomyositis sine myositis.

A 37-year-old woman with severe interstitial lung disease associated with dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed organizing diffuse alveolar damage. Significantly elevated serum levels of the tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected, but no evidence of an underlying malignancy (including breast and ovarian) was found on serial clinical and radiologic examinations. These levels gradually normalized as the interstitial lung disease responded to a combination of cyclophosphamide and corticosteroids. The use of the CA 15-3 and CASA assays to measure serum levels of the highly glycosylated, high-molecular-weight mucin MUC1 in interstitial lung disease has not been previously described. Clinicians should therefore be aware that elevation of these tumor markers may reflect the presence of interstitial lung disease rather than an underlying malignancy in patients with dermatomyositis, especially if the levels normalize after successful treatment of the lung disease.