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.

Canadian Health Care Professionals' Familiarity with Chronic Cough Guidelines and Experiences with Diagnosis and Management: A Cross-Sectional Survey.

INTRODUCTION: Educational programs on chronic cough may improve patient care, but little is known about how Canadian physicians manage this common debilitating condition. We aimed to investigate Canadian physicians' perceptions, attitudes, and knowledge of chronic cough. METHODS: We administered a 10-min anonymous, online, cross-sectional survey to 3321 Canadian physicians in the Leger Opinion Panel who managed adult patients with chronic cough and had been in practice for > 2 years. RESULTS: Between July 30 and September 22, 2021, 179 physicians (101 general practitioners [GPs] and 78 specialists [25 allergists, 28 respirologists, and 25 ear/nose/throat specialists]) completed the survey (response rate: 5.4%). In a month, GPs saw a mean of 27 patients with chronic cough, whereas specialists saw 46. About one-third of physicians appropriately identified a duration of > 8 weeks as the definition for chronic cough. Many physicians reported not using international chronic cough management guidelines. Patient referrals and care pathways varied considerably, and patients frequently experienced lost to follow-up. While physicians endorsed nasal and inhaled corticosteroids as common treatments for chronic cough, they rarely used other guideline-recommended treatments. Both GPs and specialists expressed high interest in education on chronic cough. CONCLUSION: This survey of Canadian physicians demonstrates low uptake of recent advances in chronic cough diagnosis, disease categorization, and pharmacologic management. Canadian physicians also report unfamiliarity with guideline-recommended therapies, including centrally acting neuromodulators for refractory or unexplained chronic cough. This data highlights the need for educational programs and collaborative care models on chronic cough in primary and specialist care.

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.

The Struggle to End a Millennia-Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis.

This article provides an encompassing review of the current pipeline of putative and developed treatments for tuberculosis, including multidrug-resistant strains. The review has organized each compound according to its site of activity. To provide context, mention of drugs within current recommended treatment regimens is made, thereafter followed by discussion on recently developed and upcoming molecules at established and novel targets. The review is designed to provide a clinically applicable understanding of the compounds that are deemed most currently relevant, including those already under clinical study and those that have shown promising pre-clinical results. An extensive review of the efficacy and safety data for key contemporary drugs already incorporated into treatment regimens, such as bedaquiline, pretomanid, and linezolid, is provided. The three levels of the bacterial cell wall (mycolic acid, arabinogalactan, and peptidoglycan layers) are highlighted and important compounds designed to target each layer are delineated. Amongst others, the highly optimistic and potent anti-mycobacterial activity of agents such as BTZ-043, PBTZ 169, and OPC-167832 are emphasized. The evolving spectrum of oxazolidinones, such as sutezolid, delpazolid, and TBI-223, all aiming to exceed the efficacy achieved with linezolid yet offer a safer alternative to the potential toxicity, are reviewed. New and exciting prospective agents with novel mechanisms of impact against TB, including 3-aminomethyl benzoxaboroles and telacebec, are underscored. We describe new diaryloquinolines in development, striving to build on the immense success of bedaquiline. Finally, we discuss some of these compounds that have shown encouraging additive or synergistic benefit when used in combination, providing some promise for the future in treating this ancient scourge.

Disease burden in individuals with symptomatic undiagnosed asthma or COPD.

BACKGROUND: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction. METHODS: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria. RESULTS: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism. CONCLUSION: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Derivation and validation of the UCAP-Q case-finding questionnaire to detect undiagnosed asthma and COPD.

BACKGROUND: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease. METHODS: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated. RESULTS: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD. CONCLUSIONS: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease.

Assessing cough symptom severity in refractory or unexplained chronic cough: findings from patient focus groups and an international expert panel.

Background: Cough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity. Objective: The aim of this study was to establish items and domains that would inform development of a new cough severity instrument. Methods: Three focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity. Results: The patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae). Conclusions: Consensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice.

The respiratory microbiome and nontuberculous mycobacteria: an emerging concern in human health.

Nontuberculous mycobacteria (NTM) are diverse microbial species encompassing commensals and pathogens with the ability to cause pulmonary disease in both immunocompetent and immunocompromised individuals. In contrast to Mycobacterium tuberculosis, which has seen a reduction in disease rates in developed countries, the incidence and prevalence of NTM disease is increasing. NTM are difficult to treat with standard antimicrobial regimens and may contain both virulence and antibiotic-resistance genes with potential for pathogenicity. With the advent of molecular techniques, it has been elucidated that these organisms do not reside in isolation and are rather part of a complex milieu of microorganisms within the host lung microbiome. Over the last decade, studies have highlighted the impact of the microbiome on host immunity, metabolism and cell-cell communication. This recognition of a broader community raises the possibility that the microbiome may disrupt the balance between infection and disease. Additionally, NTM disease progression and antimicrobial therapy may affect the healthy steady state of the host and function of the microbiome, contributing to further dysbiosis and clinical deterioration. There have been limited studies assessing how NTM may influence the relationship between microbiome and host. In this review, we highlight available studies about NTM and the microbiome, postulate on virulence mechanisms by which these microorganisms communicate and discuss implications for treatment.

Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure.

BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.

Population-based case-finding to identify subjects with undiagnosed asthma or COPD.

BACKGROUND: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada. METHODS: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD. RESULTS: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68). CONCLUSION: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis.

BACKGROUND: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). RESEARCH QUESTION: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. STUDY DESIGN AND METHODS: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. RESULTS: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. INTERPRETATION: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study.

Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).

Between-Visit Variability in FEV1 as a Diagnostic Test for Asthma in Adults.

RATIONALE: The reliability of using between-visit variation in forced expiratory volume in 1 second (FEV1) to diagnose asthma is understudied, and hence uncertain. OBJECTIVE: To determine whether FEV1 variability measured over recurrent visits is significantly associated with a diagnosis of current asthma. METHODS: Randomly selected adults (N = 964) with a history of physician-diagnosed asthma were studied from 2005 to 2007 and from 2012 to 2016. A diagnosis of current asthma was confirmed in those participants who exhibited bronchial hyperresponsiveness to methacholine and/or acute worsening of asthma symptoms while being weaned off asthma medications. Regression analyses and receiver operating curves were used to evaluate the ability of between-visit FEV1 variability to diagnose asthma. RESULTS: A current diagnosis of asthma was confirmed in 584 of 964 participants (60%). Between-visit absolute variability in FEV1 was significantly greater in those in whom current asthma was confirmed, compared with those in whom current asthma was ruled out (7.3% vs. 4.8%; mean difference between the two groups, 2.5%; 95% confidence interval, 1.7-3.3%). However, a 12% and 200-ml between-visit variation in FEV1, which is the diagnostic threshold recommended by Global Initiative for Asthma, exhibited a sensitivity of only 0.17 and a specificity of 0.94 for confirming current asthma. A between-visit absolute variability in FEV1 ≥ 12% and 200 ml increased the pretest probability of asthma from 60% to a posttest probability of 81%. CONCLUSIONS: A 12% and 200-ml between-visit variation in FEV1, if present, has reasonably good specificity for diagnosing asthma, but has poor sensitivity compared with bronchial challenge testing. Between-visit variability in FEV1 is a relatively unhelpful test to establish a diagnosis of asthma.

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report.

BACKGROUND: Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. METHODS: A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. RESULTS: Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. CONCLUSIONS: On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO-endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost-effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

BACKGROUND: Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. CASE PRESENTATION: We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. CONCLUSION: Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma.

Importance: Although asthma is a chronic disease, the expected rate of spontaneous remissions of adult asthma and the stability of diagnosis are unknown. Objective: To determine whether a diagnosis of current asthma could be ruled out and asthma medications safely stopped in randomly selected adults with physician-diagnosed asthma. Design, Setting, and Participants: A prospective, multicenter cohort study was conducted in 10 Canadian cities from January 2012 to February 2016. Random digit dialing was used to recruit adult participants who reported a history of physician-diagnosed asthma established within the past 5 years. Participants using long-term oral steroids and participants unable to be tested using spirometry were excluded. Information from the diagnosing physician was obtained to determine how the diagnosis of asthma was originally made in the community. Of 1026 potential participants who fulfilled eligibility criteria during telephone screening, 701 (68.3%) agreed to enter into the study. All participants were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over 4 study visits. Participants in whom a diagnosis of current asthma was ultimately ruled out were followed up clinically with repeated bronchial challenge tests over 1 year. Exposure: Physician-diagnosed asthma established within the past 5 years. Main Outcomes and Measures: The primary outcome was the proportion of participants in whom a diagnosis of current asthma was ruled out, defined as participants who exhibited no evidence of acute worsening of asthma symptoms, reversible airflow obstruction, or bronchial hyperresponsiveness after having all asthma medications tapered off and after a study pulmonologist established an alternative diagnosis. Secondary outcomes included the proportion with asthma ruled out after 12 months and the proportion who underwent an appropriate initial diagnostic workup for asthma in the community. Results: Of 701 participants (mean [SD] age, 51 [16] years; 467 women [67%]), 613 completed the study and could be conclusively evaluated for a diagnosis of current asthma. Current asthma was ruled out in 203 of 613 study participants (33.1%; 95% CI, 29.4%-36.8%). Twelve participants (2.0%) were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community. After an additional 12 months of follow-up, 181 participants (29.5%; 95% CI, 25.9%-33.1%) continued to exhibit no clinical or laboratory evidence of asthma. Participants in whom current asthma was ruled out, compared with those in whom it was confirmed, were less likely to have undergone testing for airflow limitation in the community at the time of initial diagnosis (43.8% vs 55.6%, respectively; absolute difference, 11.8%; 95% CI, 2.1%-21.5%). Conclusions and Relevance: Among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. In patients such as these, reassessing the asthma diagnosis may be warranted.

Chronic Cough Due to Gastroesophageal Reflux in Adults: CHEST Guideline and Expert Panel Report.

BACKGROUND: We updated the 2006 ACCP clinical practice guidelines for management of reflux-cough syndrome. METHODS: Two population, intervention, comparison, outcome (PICO) questions were addressed by systematic review: (1) Can therapy for gastroesophageal reflux improve or eliminate cough in adults with chronic and persistently troublesome cough? and (2) Are there minimal clinical criteria to guide practice in determining that chronic cough is likely to respond to therapy for gastroesophageal reflux? RESULTS: We found no high-quality studies pertinent to either question. From available randomized controlled trials (RCTs) addressing question #1, we concluded that (1) there was a strong placebo effect for cough improvement; (2) studies including diet modification and weight loss had better cough outcomes; (3) although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, proton pump inhibitors (PPIs) demonstrated no benefit when used in isolation; and (4) because of potential carryover effect, crossover studies using PPIs should be avoided. For question #2, we concluded from the available observational trials that (1) an algorithmic approach to management resolved chronic cough in 82% to 100% of instances; (2) cough variant asthma and upper airway cough syndrome (UACS) (previously referred to as postnasal drip syndrome) from rhinosinus conditions were the most commonly reported causes; and (3) the reported prevalence of reflux-cough syndrome varied widely. CONCLUSIONS: The panelists (1) endorsed the use of a diagnostic/therapeutic algorithm addressing causes of common cough, including symptomatic reflux; (2) advised that although lifestyle modifications and weight reduction may be beneficial in suspected reflux-cough syndrome, PPIs demonstrated no benefit when used in isolation; and (3) suggested that physiological testing be reserved for refractory patients being considered for antireflux surgery or for those in whom there is strong clinical suspicion warranting diagnostic testing.

Is Universal Screening Necessary? Incidence of Tuberculosis among Tibetan Refugees Arriving in Calgary, Alberta.

Background. Canadian policy requires refugees with a history of tuberculosis (TB) or abnormal chest radiograph to be screened after arrival for TB. However, Tibetan refugees are indiscriminately screened, regardless of preimmigration assessment. We sought to determine the incidence of latent (LTBI) and active TB, as well as treatment-related outcomes and associations between preimmigration factors and TB infection among Tibetan refugees arriving in Calgary, Alberta. Design. Retrospective cohort study including Tibetan refugees arriving between 2014 and 2016. Associations between preimmigration factors and incidence of latent and active TB were determined using Chi-square tests. Results. Out of 180 subjects, 49 percent had LTBI. LTBI was more common in migrants 30 years of age or older (P = 0.009). Treatment initiation and completion rates were high at 90 percent and 76 percent, respectively. No associations between preimmigration factors and treatment completion were found. A case of active TB was detected and treated. Conclusion. Within this cohort, the case of active TB would have been detected through the usual postsurveillance process due to a history of TB and abnormal chest radiograph. Forty-nine percent had LTBI, compared to previously quoted rates of 97 percent. Tibetan refugees should be screened for TB in a similar manner to other refugees resettling in Canada.