Simon Martel

Probability of Cancer in Pulmonary Nodules Detected on First Screening CT

BACKGROUND Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension

Background A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite new specific therapies. Whether patients with IPAH exhibit peripheral muscle dysfunction that may contribute to this limitation remains unknown. The hypothesis that the muscles of patients with IPAH are weaker and display morphological changes compared with those of control subjects and that those changes partly correlate with their exercise capacity was tested. Objective To characterise quadriceps function, morphology and the enzymatic profile of patients with IPAH. Methods Exercise capacity, limb muscle cross-sectional area by CT scan, quadriceps strength by maximal voluntary contraction and non-volitional magnetic stimulation of the femoral nerve (quadriceps twitch; TWq), and muscle morphology and enzymatic profile by quadriceps biopsy of 10 patients with IPAH were compared with those of 10 matched controls subjects. Results Patients with IPAH displayed a lower proportion of type I muscle fibres (p=0.05), a lower maximal voluntary contraction (p=0.05) and TWq (p=0.01), and an increased muscular phosphofructokinase/3-hydroxyacyl-CoA-dehydrogenase ratio (p=0.05). They also tended to have lower thigh muscle cross-sectional area (p=0.15). Maximal oxygen uptake correlated with quadriceps strength (R2=0.42, p=0.04), and oxygen uptake at anaerobic threshold correlated with muscle oxidative capacity assessed by oxidative enzyme level for citrate synthase (R2=0.45, p=0.05) and 3-hydroxyacyl-CoA-dehydrogenase (R2=0.86, p<0.01), and type I fibre capillarity (R2=0.57, p=0.02). Conclusion Patients with IPAH present significant peripheral muscle changes that partly correlated with their exercise capacity.

Effects of a rehabilitation program on skeletal muscle function in idiopathic pulmonary arterial hypertension.

INTRODUCTION: A majority of patients with idiopathic pulmonary arterial hypertension (IPAH) display persistent exercise intolerance despite current therapies. Whether a rehabilitation program elicits favorable changes in muscle function which would partly explain improvements in exercise tolerance of IPAH patients remains unknown. We performed this study to assess the effect of a 12-week rehabilitation program on skeletal muscle characteristics and exercise tolerance in patients with IPAH. METHODS: Exercise capacity measured by the 6-minute walk test and by the cycle endurance test (CET), limb muscle cross-sectional area, quadriceps function by maximal voluntary contraction and magnetic stimulation (potentiated twitches), and molecular muscle characteristics by quadriceps biopsy of 5 IPAH patients were assessed before and after a 12-week rehabilitation program. RESULTS: Following training, improvements in all patients were observed for the 6-minute walk test distance, from 441 (75) to 499 (85) m, P = .01, and the CET time, from 429 (239) to 633 (380) seconds, P = .16. Minute ventilation assessed at isotime during CET decreased by 15(11)%, P = .05. This was related to both decreased carbon dioxide output and . These improvements were associated with decreased type IIx fiber proportion, 31(8)% to 23(10)%, P = .05. DISCUSSION: Peripheral muscle characteristic improvements may contribute to the clinical benefit observed following a rehabilitation program in IPAH.

Effects of Bronchial Thermoplasty on Airway Smooth Muscle and Collagen Deposition in Asthma

RATIONALE The aim of bronchial thermoplasty is to improve asthma symptoms by reducing central airway smooth muscle mass. Up to now, the reduction of smooth muscle mass has been documented for only 1 group of 10 patients who had 15% or more of their pretreatment total bronchial biopsy area occupied by smooth muscle. OBJECTIVES To evaluate the effects of bronchial thermoplasty on airway smooth muscle mass and airway collagen deposition in adult patients with asthma, regardless of pretreatment smooth muscle area. METHODS Seventeen patients with asthma underwent bronchial thermoplasty over the course of three visits. At Visit 1, bronchial biopsies were taken from the lower lobe that was not treated during this session. At Visit 2 (3-14 wk after the first visit), all 17 patients underwent biopsy of the lower lobe treated during the first procedure. At Visit 3 (7-22 wk after the first visit), nine patients agreed to undergo biopsy of the same lower lobe. Histological and immunohistochemical analyses were performed on the biopsy specimens. MEASUREMENTS AND MAIN RESULTS Bronchial thermoplasty decreased airway smooth muscle from 12.9 ± 1.2% of the total biopsy surface at Visit 1 to 4.6 ± 0.8% at Visit 2 (P < 0.0001). For the nine patients who underwent a third biopsy, mean airway smooth muscle area was 5.3 ± 1.3% at Visit 3 (P = 0.0008 compared with baseline). Bronchial thermoplasty also decreased Type I collagen deposition underneath the basement membrane from 6.8 ± 0.3 μm at Visit 1 to 4.3 ± 0.2 μm at Visit 2 (P < 0.0001) and to 4.4 ± 0.4 μm for nine patients at Visit 3 (P < 0.0001 compared with baseline). Over the course of 1 year after treatment, the doses of inhaled corticosteroid, the number of severe exacerbations, and asthma control all improved (P ≤ 0.02). CONCLUSIONS For patients with severe asthma, bronchial thermoplasty reduced the smooth muscle mass of treated airway segments, regardless of the baseline level of muscle mass. Treatment also altered the deposition of collagen. At follow-up, bronchial thermoplasty improved asthma control; however, the limited number of subjects did not allow us to evaluate possible correlations between these improvements and the studied histological parameters. Further studies are needed to confirm these results and evaluate their persistence.

Diagnostic utility of peripheral endobronchial ultrasound with electromagnetic navigation bronchoscopy in peripheral lung nodules

This study aimed to investigate the diagnostic utility of peripheral endobronchial ultrasound (pEBUS) followed by as‐needed electromagnetic navigation bronchoscopy (ENB) for sampling peripheral lung nodules.

Adaptation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) into French-Canadian and English-Canadian.

BACKGROUND The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for assessing patient-reported symptoms, functioning and quality of life (QoL) in pulmonary arterial hypertension (PAH). OBJECTIVES To create and validate French-Canadian (FC) and English-Canadian (EC) language versions of the CAMPHOR. METHODS A translation panel (for the FC version) and lay panels (for both versions) were convened to adapt the questionnaires (dual-panel methodology). Subsequently, these new questionnaires were field-tested in 15 FC PAH and 15 EC PAH patients. Finally, in a postal validation study, the new language versions of the CAMPHOR underwent psychometric evaluation in 41 FC and 52 EC PAH patients to test for reliability and validity. RESULTS The FC and EC field-test interview participants found the questionnaires relevant, comprehensible and easy to complete. Psychometric analyses showed that the FC and EC adaptations were successful. High test-retest coefficients for the scales after controlling for change in respondents QoL (FC: 0.92 to 0.96; EC: 0.85 to 0.99) indicated a high degree of reliability. The FC and EC CAMPHOR scales had good internal consistency (Cronbachs alpha coefficients 0.90 to 0.92 and 0.88 to 0.92, respectively). Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the FC and EC scales. The FC and EC adaptations also showed known groups validity. CONCLUSIONS The FC and EC adaptations of the CAMPHOR have been shown to be reliable and valid for measures of health-related QoL and QoL in PAH, and thus can be recommended for use in clinical studies and routine practice in PAH.

Resource utilization and costs during the initial years of lung cancer screening with computed tomography in Canada.

Background: It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Methods: Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer’s perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. Results: The average per-person cost for screening individuals with LDCT was

The Cost-Effectiveness of High-Risk Lung Cancer Screening and Drivers of Program Efficiency

453 (95% confidence interval [CI],

Tumour necrosis factor-alpha gene expression by alveolar macrophages in human lung allograft recipient with recurrence of sarcoidosis. Toulouse Lung Transplantation Group

400–

Plasma pro-surfactant protein B and lung function decline in smokers

505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was