Early Diagnosis and Treatment of COPD and Asthma - A Randomized, Controlled Trial.

BACKGROUND: Many persons with chronic obstructive pulmonary disease (COPD) or asthma have not received a diagnosis, so their respiratory symptoms remain largely untreated. METHODS: We used a case-finding method to identify adults in the community with respiratory symptoms without diagnosed lung disease. Participants who were found to have undiagnosed COPD or asthma on spirometry were enrolled in a multicenter, randomized, controlled trial to determine whether early diagnosis and treatment reduces health care utilization for respiratory illness and improves health outcomes. Participants were assigned to receive the intervention (evaluation by a pulmonologist and an asthma-COPD educator who were instructed to initiate guideline-based care) or usual care by their primary care practitioner. The primary outcome was the annualized rate of participant-initiated health care utilization for respiratory illness. Secondary outcomes included changes from baseline to 1 year in disease-specific quality of life, as assessed with the St. George Respiratory Questionnaire (SGRQ; scores range from 0 to 100, with lower scores indicating better health status); symptom burden, as assessed with the COPD Assessment Test (CAT; scores range from 0 to 40, with lower scores indicating better health status); and forced expiratory volume in 1 second (FEV1). RESULTS: Of 38,353 persons interviewed, 595 were found to have undiagnosed COPD or asthma and 508 underwent randomization: 253 were assigned to the intervention group and 255 to the usual-care group. The annualized rate of a primary-outcome event was lower in the intervention group than in the usual-care group (0.53 vs. 1.12 events per person-year; incidence rate ratio, 0.48; 95% confidence interval [CI], 0.36 to 0.63; P<0.001). At 12 months, the SGRQ score was lower than the baseline score by 10.2 points in the intervention group and by 6.8 points in the usual-care group (difference, -3.5 points; 95% CI, -6.0 to -0.9), and the CAT score was lower than the baseline score by 3.8 points and 2.6 points, respectively (difference, -1.3 points; 95% CI, -2.4 to -0.1). The FEV1 increased by 119 ml in the intervention group and by 22 ml in the usual-care group (difference, 94 ml; 95% CI, 50 to 138). The incidence of adverse events was similar in the trial groups. CONCLUSIONS: In this trial in which a strategy was used to identify adults in the community with undiagnosed asthma or COPD, those who received pulmonologist-directed treatment had less subsequent health care utilization for respiratory illness than those who received usual care. (Funded by Canadian Institutes of Health Research; UCAP ClinicalTrials.gov number, NCT03148210.).

A Statistical Testing Strategy Accounting for Random and Nonrandom (Skewed) X-Chromosome Inactivation Identifies Lung Cancer Susceptibility Loci among Smokers.

INTRODUCTION: Lung cancer is the most common cancer worldwide in mortality and the second in incidence. Epidemiological studies found a higher lung cancer risk for smoking women in comparison to men, but these sex differences, irrespective of smoking habits, remain controversial. One of the hypotheses concerns the genetic contribution of the sex chromosomes. However, while genome-wide association studies identified many lung cancer susceptibility loci, these analyses have excluded X-linked loci. METHODS: To account for nongenetic factors, we first presented an association test based on an additive-multiplicative hazard model accounting for random/nonrandom X-inactivation process. A simulation study was performed to investigate the properties of the proposed test as compared with the Wald test from a Cox model with random X-inactivation process and the partial likelihood ratio test proposed by Xu et al. accounting for nonrandom X-inactivation process. Then, we performed an X chromosome-wide association study on 9,261 individuals from the population-based cohort CARTaGENE to identify susceptibility loci for lung cancer among current and past smokers. We adjusted for the PLCOm2012 lung cancer risk score used in screening programs. RESULTS: Simulation results show the good behavior of the proposed test in terms of power and type I error probability as compared to the Xu et al. and the Wald test. Using the proposed test statistic and adjusting for the PLCOm2012 score, the X chromosome-wide statistical analysis identified two SNPs in low-linkage disequilibrium located in the IL1RAPL1 (IL-1 R accessory protein-like) gene: rs12558491 (p = 2.75×10-9) and rs12835699 (p = 1.26×10-6). For both SNPs, the minor allele was associated with lower lung cancer risk. Adjusting for multiple testing, no signal was detected using the Wald or the Xu et al. likelihood ratio tests. CONCLUSION: By taking into account smoking behavior and the X-inactivation process, the investigation of the X chromosome has shed a new light on the association between X-linked loci and lung cancer. We identified two loci associated with lung cancer located in the IL1RAPL1 gene. This finding would have been overlooked by examining only results from other test statistics.

Association between lung function and sleep disorder symptoms in a community-based multi-site case-finding study.

Obstructive airway disease is associated with sleep disturbances. We aimed to assess the relationship between lung function and sleep disorder symptoms using cross-sectionally collected data between March 2017 and August 2021 from the Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study, a prospective community-based multi-site case-finding study. Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study participants with respiratory symptoms but without diagnosed lung disease who completed spirometry and the Global Sleep Assessment Questionnaire were included. We conducted multivariate linear regression models for forced expiratory volume in 1 s, forced vital capacity and forced expiratory volume in 1 s/forced vital capacity by Global Sleep Assessment Questionnaire responses adjusted for confounders. The same models were employed to examine respiratory symptoms, as reported on the St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test, by Global Sleep Assessment Questionnaire responses. Logistic regression models were used to assess the association of undiagnosed obstructive airway disease with sleep symptoms. Amongst 2093 adults included in the study, 48.3% were female and the median age was 63 years (interquartile range 53-72). Two-hundred and five (9.79%) subjects met spirometry criteria for undiagnosed chronic obstructive pulmonary disease, and 191 (9.13%) for undiagnosed asthma. There were no significant associations between spirometry measures and sleep symptoms (p > 0.5), controlling for age, sex, body mass index, smoking and comorbidities. Those with undiagnosed asthma were more likely to report insomnia "at least sometimes" versus "never" (odds ratio 2.58, 95% confidence interval: 1.27-6.19, p = 0.02). Respiratory symptoms were associated with sleep symptoms, with significant (p < 0.05) increases in St George's Respiratory Questionnaire and Chronic Obstructive Pulmonary Disease Assessment Test scores in those reporting most sleep symptoms. Overall, we found an association between undiagnosed asthma and insomnia, and between respiratory and sleep disorder symptoms.

Nunavimmi puvakkut kaggutimik aanniaqarniq: Qanuilirqitaa? Lung cancer in Nunavik: How are we doing? A retrospective matched cohort study.

BACKGROUND: Whether Inuit in Canada experience disparities in lung cancer survival remains unknown. When requiring investigation and treatment for lung cancer, all residents of Nunavik, the Inuit homeland in Quebec, are sent to the McGill University Health Centre (MUHC), in Montréal. We sought to compare survival among patients with lung cancer at the MUHC, who were residents of Nunavik and Montréal, Quebec, respectively. METHODS: We conducted a retrospective cohort study. Using lung cancer registry data, we identified Nunavik residents with histologically confirmed lung cancer diagnosed between 2005 and 2017. We aimed to match 2 Montréal residents to each Nunavik resident on sex, age, calendar year of diagnosis, and histology (non-small cell lung cancer v. small cell lung cancer). We reviewed medical records for data on additional patient characteristics and treatment, and obtained vital status from a provincial registry. We compared survival using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: We included 95 residents of Nunavik and 185 residents of Montréal. For non-small cell lung cancer, median survival times were 321 (95% confidence interval [CI] 184-626) days for Nunavik (n = 71) and 720 (95% CI 536-1208) days for Montréal residents (n = 141). For small cell lung cancer, median survival times were 190 (95% CI 159-308) days for Nunavik (n = 24) and 270 (95% CI 194-766) days for Montréal residents (n = 44). Adjusting for matching variables, stage, performance status, and comorbidity, Nunavik residents had a higher hazard of death (hazard ratio 1.68, 95% CI 1.17-2.41). INTERPRETATION: Nunavik residents experience disparities in survival after lung cancer diagnosis. Although studies in other Inuit Nunangat regions are needed, our findings point to an urgent need to ensure that interventions aimed at improving lung cancer survival, including lung cancer screening, are accessible to Inuit Nunangat residents.

Development of a clinical risk score for the prediction of Pneumocystis jirovecii pneumonia in hospitalised patients.

BACKGROUND: The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-ß-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. METHODS: The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score's receiver operating characteristic curve. RESULTS: Participants had a median age of 60 years (interquartile range [IQR] 49-68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71-0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. CONCLUSION: We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Impact of Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma on Symptoms, Quality of Life, Healthcare Use, and Work Productivity.

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19 : A Randomized Platform Trial.

BACKGROUND: Previous trials have demonstrated the effects of fluvoxamine alone and inhaled budesonide alone for prevention of disease progression among outpatients with COVID-19. OBJECTIVE: To determine whether the combination of fluvoxamine and inhaled budesonide would increase treatment effects in a highly vaccinated population. DESIGN: Randomized, placebo-controlled, adaptive platform trial. (ClinicalTrials.gov: NCT04727424). SETTING: 12 clinical sites in Brazil. PARTICIPANTS: Symptomatic adults with confirmed SARS-CoV-2 infection and a known risk factor for progression to severe disease. INTERVENTION: Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) plus inhaled budesonide (800 mcg twice daily for 10 days) or matching placebos. MEASUREMENTS: The primary outcome was a composite of emergency setting retention for COVID-19 for more than 6 hours, hospitalization, and/or suspected complications due to clinical progression of COVID-19 within 28 days of randomization. Secondary outcomes included health care attendance (defined as hospitalization for any cause or emergency department visit lasting >6 hours), time to hospitalization, mortality, patient-reported outcomes, and adverse drug reactions. RESULTS: Randomization occurred from 15 January to 6 July 2022. A total of 738 participants were allocated to oral fluvoxamine plus inhaled budesonide, and 738 received placebo. The proportion of patients observed in an emergency setting for COVID-19 for more than 6 hours or hospitalized due to COVID-19 was lower in the treatment group than the placebo group (1.8% [95% credible interval {CrI}, 1.1% to 3.0%] vs. 3.7% [95% CrI, 2.5% to 5.3%]; relative risk, 0.50 [95% CrI, 0.25 to 0.92]), with a probability of superiority of 98.7%. No relative effects were found between groups for any of the secondary outcomes. More adverse events occurred in the intervention group than the placebo group, but no important differences between the groups were detected. LIMITATION: Low event rate overall, consistent with contemporary trials in vaccinated populations. CONCLUSION: Treatment with oral fluvoxamine plus inhaled budesonide among high-risk outpatients with early COVID-19 reduced the incidence of severe disease requiring advanced care. PRIMARY FUNDING SOURCE: Latona Foundation, FastGrants, and Rainwater Charitable Foundation.

Patient and physician factors associated with symptomatic undiagnosed asthma or COPD.

BACKGROUND: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD. METHODS: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD. RESULTS: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97). CONCLUSIONS: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.

Development and application of an electronic synoptic report for reporting and management of low-dose computed tomography lung cancer screening examination.

BACKGROUND: Interpretation of Low Dose CT scans and protocol driven management of findings is a key aspect of lung cancer screening program performance. Reliable and reproducible methods are needed to communicate radiologists' interpretation to the screening program or clinicians driving management decision. METHODS: We performed an audit of a subset of dictated reports from the PANCAN study to assess for omissions. We developed an electronic synoptic reporting tool for radiologists embedded in a clinical documentation system software. The tool was then used for reporting as part of the Alberta Lung Cancer Screening Study and McGill University Health Centre Pilot Lung Cancer Screening Program. RESULTS: Fifty reports were audited for completeness. At least one omission was noted in 30 (70%) of reports, with a major omission (missing lobe, size, type of nodule in report or actionable incidental finding in recommendation section of report) in 24 (48%). Details of the reporting template and functionality such as automated nodule cancer risk assessment, Lung-RADS category assignment, auto-generated narrative type report as well as personalize participant results letter is provided. A description of the system's performance in its application in 2815 CT reports is then summarized. CONCLUSIONS: We found that narrative type radiologist reports for lung cancer screening CT examinations frequently lacked specific discrete data elements required for management. We demonstrate the successful implementation of a radiology synoptic reporting system for use in lung cancer screening, and the use of this information to drive program management and communications.

Racial Disparities in Resection of Early Stage Non-Small Cell Lung Cancer: Variability Among Surgeons.

BACKGROUND: Racial disparities in resection of non-small cell lung cancer (NSCLC) are well documented. Patient-level and system-level factors only partially explain these findings. Although physician-related factors have been suggested as mediators, empirical evidence for their contribution is limited. OBJECTIVE: To determine if racial disparities in receipt of thoracic surgery persisted after patients had a surgical consultation and whether there was a physician contribution to disparities in care. METHODS: The authors identified 19,624 patients with stage I-II NSCLC above 65 years of age from the Surveillance-Epidemiology and End-Results-Medicare database. They studied black and white patients evaluated by a surgeon within 6 months of diagnosis. They assessed for racial differences in resection rates among surgeons using hierarchical linear modeling. Our main outcome was receipt of NSCLC resection. A random intercept was included to test for variability in resection rates across surgeons. Interaction between patient race and the random surgeon intercept was used to evaluate for heterogeneity between surgeons in resection rates for black versus white patients. RESULTS: After surgical consultation, black patients were less likely to undergo resection (adjusted odds ratio, 0.57; 95% confidence interval, 0.47-0.69). Resection rates varied significantly between surgeons (P<0.001). A significant interaction between the surgeon intercept and race (P<0.05) showed variability beyond chance across surgeons in resection rates of black versus white patients. When the model included thoracic surgery specifalization the physician contribution to disparities in care was decreased. CONCLUSIONS: Racial disparities in resection of NSCLC exist even among patients who had access to a surgeon. Heterogeneity between surgeons in resection rates between black and white patients suggests a physician's contribution to observed racial disparities. Specialization in thoracic surgery attenuated this contribution.

Primary lung cancer diagnoses in people living with HIV in a large clinical centre in Montreal, Canada over 3 decades.

Lung cancer is the most frequent type of cancer-related death in people living with HIV (PLWH). We conducted a review of primary lung cancers in PLWH at the McGill University Health Centre from 1988-May 2018 to understand potential factors contributing to their development prior to the implementation of a lung cancer screening program. Twenty-seven individuals had a diagnosis of a lung tumor. Of these individuals, 21 (78%) had a primary lung cancer, over 21,428 person-years follow-up. Median age was 54.5 years [25th and 75th percentiles 49.0, 62.0]. Median CD4 count was 185.0 cells/µL [25th and 75th percentiles 54.0, 446.0] and 52% were on antitretroviral therapy with suppressed viral loads. Type of primary lung cancer included: non-small cell lung cancer (n = 15), small-cell lung cancer (n = 4) and bronchial carcinomas (n = 2). Metastatic disease at diagnosis was present in 11 (52%) persons. Survival was a median of 7.5 months from the time of diagnosis [25th and 75th percentiles 2.0, 9.0]. In conclusion, we observed a high proportion of lung cancers detected at very late stages of disease and with metastatic involvement. The implementation of a lung cancer screening program in 2018 should set a stage shift for earlier diagnosis and treatment.

Radiographic features in investigated for Pneumocystis jirovecii pneumonia: a nested case-control study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) can be challenging to diagnose, often requiring bronchoscopy. Since most patients suspected of PJP undergo imaging, we hypothesized that the findings of these studies could help estimate the probability of disease prior to invasive testing. METHODS: We created a cohort of patients who underwent bronchoscopy specifically to diagnose PJP and conducted a nested case-control study to compare the radiographic features between patients with (n = 72) and without (n = 288) pathologically proven PJP. We used multivariable logistic regression to identify radiographic features independently associated with PJP. RESULTS: Chest x-ray findings poorly predicted the diagnosis of PJP. However, multivariable analysis of CT scan findings found that "increased interstitial markings" (OR 4.3; 95%CI 2.2-8.2), "ground glass opacities" (OR 3.3; 95%CI 1.2-9.1) and the radiologist's impression of PJP being "possible" (OR 2.0; 95%CI 1.0-4.1) or "likely" (OR 9.3; 95%CI 3.4-25.3) were independently associated with the final diagnosis (c-statistic 0.75). CONCLUSIONS: Where there is clinical suspicion of PJP, the use of CT scan can help determine the probability of PJP. Identifying patients at low risk of PJP may enable better use of non-invasive testing to avoid bronchoscopy while higher probability patients could be prioritized.

Description of Participation in Daily and Social Activities for Individuals with COPD.

This study described the participation in daily and social activities and the perceived barriers and facilitators to participation of individuals with chronic obstructive pulmonary disease (COPD). Individuals, recruited from outpatient clinics, responded to a survey on their participation in, and barriers and facilitators towards, 26 daily and social activities, divided into 3 categories: (1) physical activity and movement (PAM); (2) self-care; and (3) social engagement. For each activity, chi-square analyses were used to examine participation differences by individuals': quartiles of airflow obstruction [percent predicted forced expiratory volume in 1 second (FEV1%predicted)] and breathlessness burden and exacerbation risk. Of the 200 participants (47% women; mean ± standard deviation age = 68 ± 9 years), most wanted to increase their participation in PAM activities (range 21-75%) and significant differences were found in 5/10 PAM activities for individuals' breathlessness burden and exacerbation risk (e.g., more individuals than expected in group A (modified Medical Research Council breathlessness score <2 and 0-1 exacerbations in past 12 months) participated in regular exercise as much as they wanted (χ(9)2=20.43, Cramer's V=.23)). Regardless of the degree of airflow obstruction or breathlessness burden and exacerbation risk, the most common barrier to participation was breathlessness (p<.001, η2p=.86) and the most common facilitator was engaging as part of their routine (p<.001, η2p=.75). Individuals with COPD want to increase their participation in daily and social activities but are limited by breathlessness. Strategies to alleviate breathlessness should be identified/prioritized and incorporated into individuals' daily routines to meet their self-reported participation objectives in daily and social activities.

Impact of rapid investigation clinic on timeliness of lung cancer diagnosis and treatment.

BACKGROUND: Guidelines recommend timely evaluation of patients with suspected lung cancer. We evaluated the impact of a Rapid Investigation Clinic (RIC) on timeliness of lung cancer diagnosis and treatment between February 2010 and December 2011. METHODS: Investigation within the RIC was conducted by a pulmonologist and a nurse clinician. Controls were patients with lung cancer, investigated outside the RIC at the same institution during the same time period. The primary outcome was time between first contact with a local physician for suspected lung cancer (T0) and first treatment. Factors associated with the delay from T0 to first treatment were examined using multivariate analysis. Completeness of lung cancer staging according to guidelines was assessed. RESULTS: A total of 195 patients were investigated within the RIC vs. 132 patients outside the RIC. The median delay between T0 and first treatment was 65 days (interquartile range [IQR] 46-92 days) in the RIC and 78 days (IQR 49-119 days) in the non-RIC patients (p ≤ 0.01). Time from T0 to pathological diagnosis was shorter in the RIC (median 26 days; IQR 14-42 days) vs. non-RIC patients (median 40 days; IQR 16-68 days). In multivariate analysis, investigation in the RIC was associated with a reduction in time to first treatment of 24 days (95% confidence interval [CI] 12-35 days) when adjusted for relevant confounders. Guideline-concordant investigation occurred more frequently in RIC patients, based on the quality indicators examined. CONCLUSIONS: A Rapid Investigation Clinic reduces delays to lung cancer diagnosis and treatment, and impacts quality of care.

Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Trends and Surgical Outcomes in a Regionalized Pulmonary Oncology Network.

BACKGROUND: Several regulatory agencies have approved the use of the neoadjuvant chemo-immunotherapy for resectable stage II and III of non-small cell lung cancer (NSCLC) and numerous trials investigating novel agents are underway. However, significant concerns exist around the feasibility and safety of offering curative surgery to patients treated within such pathways. The goal in this study was to evaluate the impact of a transition towards a large-scale neoadjuvant therapy program for NSCLC. METHODS: Medical charts of patients with clinical stage II and III NSCLC who underwent resection from January 2015 to December 2020 were reviewed. The primary outcome was perioperative complication rate between neoadjuvant-treated versus upfront surgery patients. Multivariable logistic regression estimated occurrence of postoperative complications and overall survival was assessed as an exploratory secondary outcome by Kaplan-Meier and Cox-regression analyses. RESULTS: Of the 428 patients included, 106 (24.8%) received neoadjuvant therapy and 322 (75.2%) upfront surgery. Frequency of minor and major postoperative complications was similar between groups (P = .22). Occurrence in postoperative complication was similar in both cohort (aOR = 1.31, 95% CI 0.73-2.34). Neoadjuvant therapy administration increased from 10% to 45% with a rise in targeted and immuno-therapies over time, accompanied by a reduced rate of preoperative radiation therapy use. 1-, 2-, and 5-year overall survival was higher in neoadjuvant therapy compared to upfront surgery patients (Log-Rank P = .017). CONCLUSIONS: No significant differences in perioperative outcomes and survival were observed in resectable NSCLC patients treated by neoadjuvant therapy versus upfront surgery. Transition to neoadjuvant therapy among resectable NSCLC patients is safe and feasible from a surgical perspective.

Impact of Dyspnea on Adults With Respiratory Symptoms Without a Defined Diagnosis.

BACKGROUND: We investigated dyspnea, its associated risk factors, and its impact on health care utilization, quality of life, and work productivity in adults with undiagnosed respiratory symptoms. RESEARCH QUESTION: What is the impact of dyspnea in adults with undiagnosed respiratory symptoms? STUDY DESIGN AND METHODS: This population-based study included 2,857 adults who were experiencing respiratory symptoms. These individuals had not been previously diagnosed with any lung conditions and were recruited from 17 Canadian centers using random digit dialing. Each participant underwent spirometry testing both before and after using a bronchodilator to determine if they met the diagnostic criteria for COPD, asthma, or preserved ratio impaired spirometry (PRISm), or if their spirometry results were normal. An age-matched control group (n = 231) was similarly recruited using random digit dialing. A dyspnea impact assessment score from 0 to 100 was produced using questions from the COPD Assessment Test and St. George's Respiratory questionnaire. RESULTS: Individuals with PRISm (n = 172) reported more impactful dyspnea (mean score, 63.0; 95% CI, 59.5-66.4) than those with undiagnosed asthma (n = 265; mean score, 56.6; 95% CI, 53.9-59.3) or undiagnosed COPD (n = 330; mean score, 57.5; 95% CI, 55.1-59.9). All groups reported significantly more impactful dyspnea than the control group (mean score, 13.8; 95% CI, 11.8-15.7). Patient-specific risk factors including age, sex, BMI, smoking, and comorbidities explained 20.6% of the variation in dyspnea. An additional 12.4% of the variation was explained by disease classification and another 1.7% by the severity of lung function impairment assessed with spirometry. After adjusting for age, sex, and BMI, greater dyspnea impact was associated with increased health care utilization, lower quality of life, and reduced work productivity. INTERPRETATION: In community-based adults with undiagnosed respiratory symptoms, those identified with PRISm experienced the greatest impact of dyspnea. Dyspnea imposes burdens on the health care system and is associated with impaired quality of life and work productivity.

Evaluation of the accuracy of the PLCOm2012 6-year lung cancer risk prediction model among smokers in the CARTaGENE population-based cohort.

BACKGROUND: The PLCOm2012 prediction tool for risk of lung cancer has been proposed for a pilot program for lung cancer screening in Quebec, but has not been validated in this population. We sought to validate PLCOm2012 in a cohort of Quebec residents, and to determine the hypothetical performance of different screening strategies. METHODS: We included smokers without a history of lung cancer from the population-based CARTaGENE cohort. To assess PLCOm2012 calibration and discrimination, we determined the ratio of expected to observed number of cases, as well as the sensitivity, specificity and positive predictive values of different risk thresholds. To assess the performance of screening strategies if applied between Jan. 1, 1998, and Dec. 31, 2015, we tested different thresholds of the PLCOm2012 detection of lung cancer over 6 years (1.51%, 1.70% and 2.00%), the criteria of Quebec's pilot program (for people aged 55-74 yr and 50-74 yr) and recommendations from 2021 United States and 2016 Canada guidelines. We assessed shift and serial scenarios of screening, whereby eligibility was assessed annually or every 6 years, respectively. RESULTS: Among 11 652 participants, 176 (1.51%) lung cancers were diagnosed in 6 years. The PLCOm2012 tool underestimated the number of cases (expected-to-observed ratio 0.68, 95% confidence interval [CI] 0.59-0.79), but the discrimination was good (C-statistic 0.727, 95% CI 0.679-0.770). From a threshold of 1.51% to 2.00%, sensitivities ranged from 52.3% (95% CI 44.6%-59.8%) to 44.9% (95% CI 37.4%-52.6%), specificities ranged from 81.6% (95% CI 80.8%-82.3%) to 87.7% (95% CI 87.0%-88.3%) and positive predictive values ranged from 4.2% (95% CI 3.4%-5.1%) to 5.3% (95% CI 4.2%-6.5%). Overall, 8938 participants had sufficient data to test performance of screening strategies. If eligibility was estimated annually, Quebec pilot criteria would have detected fewer cancers than PLCOm2012 at a 2.00% threshold (48.3% v. 50.2%) for a similar number of scans per detected cancer. If eligibility was estimated every 6 years, up to 26 fewer lung cancers would have been detected; however, this scenario led to higher positive predictive values (highest for PLCOm2012 with a 2.00% threshold at 6.0%, 95% CI 4.8%-7.3%). INTERPRETATION: In a cohort of Quebec smokers, the PLCOm2012 risk prediction tool had good discrimination in detecting lung cancer, but it may be helpful to adjust the intercept to improve calibration. The implementation of risk prediction models in some of the provinces of Canada should be done with caution.

Impact of Volume on Mortality and Hospital Stay After Lung Cancer Surgery in a Single-Payer System.

BACKGROUND: There is a literature gap for hospitals in single-payer health care systems quantifying the influence of hospital volume on outcomes after major lung cancer resection. We aimed to determine the effect of hospital volume on mortality and length of stay. METHODS: A retrospective cohort study using administrative, population-based data from a single-payer universal health care system was performed in adults with non-small cell lung cancer who underwent lobectomy or pneumonectomy between 2008 and 2017. Hospital volume was defined as the average annual number of major lung resections performed at each institution. Length of stay and postoperative mortality were compared using multivariable linear and nonlinear regression between hospital volume categories and continuously. Adjusted association between hospital volume and postoperative mortality was determined by multivariable logistic regression. RESULTS: In all, 10 831 lung resections were performed: 1237 pneumonectomies and 9594 lobectomies. Patients undergoing lobectomy at high-volume hospitals had shorter median length of stay (6 vs 8 days, P = .001) compared with low-volume hospitals. After adjusting for confounders, surgery at a high-volume center was significantly associated with shorter length of stay after lobectomy and overall resections (P ≤ .001), but not after pneumonectomy (P = .787). Surgery at a high-volume center was positively associated with improved 90-day mortality in lobectomy and overall procedures (odds ratio 0.607 [95% confidence interval, 0.399 to 0.925], and 0.632 [95% confidence interval, 0.441 to 0.904], respectively). Volume was not a predictor of 90-day mortality after pneumonectomy (odds ratio 0.533 [95% confidence interval, 0.257 to 1.104], P = .090). CONCLUSIONS: Surgery at a high-volume center was positively correlated with improved 90-day survival and shorter hospital length of stay. The results support regionalized lung cancer care in a single-payer health care system.

Smoking Cessation by Phone Counselling in a Lung Cancer Screening Program: A Retrospective Comparative Cohort Study.

Introduction: Smoking cessation integration within lung cancer screening programs is challenging. Currently, phone counselling is available across Canada for individuals referred by healthcare workers and by self-referral. We compared quit rates after phone counselling interventions between participants who self-refer, those referred by healthcare workers, and those referred by a lung cancer screening program. Methods: This is a retrospective cohort study of participants referred to provincial smoking cessation quit line in contemporaneous cohorts: self-referred participants, healthcare worker referred, and those referred by a lung cancer screening program if they were still actively smoking at the time of first contact. Baseline, covariates (sociodemographic information, smoking history, and history of mental health disorder) and quit intentions (stage of change, readiness for change, previous use of quit programs, and previous quit attempts) were compared among the three cohorts. Our primary outcome was defined as self-reported 30-day abstinence rates at 6 months. Multivariable logistic regression was used to identify whether group assignment was associated with higher quit rates. Results: Participants referred by a lung cancer screening program had low quit rates (12%, 95% CI: 5-19) at six months despite the use of phone counselling. Compared to patients who were self-referred to the smoking cessation phone helpline, individuals referred by a lung cancer screening program were much less likely to quit (adjusted OR 0.37; 95% CI: 0.17-0.8), whereas those referred by healthcare workers were twice as likely to quit (adjusted OR 2.16 (1.3-3.58)) even after adjustment for differences in smoking intensity and quit intentions. Conclusions: Phone counselling alone has very limited benefit in a lung cancer screening program. Participants differ significantly from those who are otherwise referred by healthcare workers. This study underlines the importance of a dedicated and personalized tobacco treatment program within every lung cancer screening program. The program should incorporate best practices and encourage treatment regardless of readiness to quit.