Psychological consequences of MRI-based screening among women with strong family histories of breast cancer.

PURPOSE: MRI-based screening in women with a ≥ 25% lifetime risk of breast cancer , but no identifiable genetic mutations may be associated with false positives. This study examined the psychological impact of abnormal screens and biopsies in non-mutation carriers participating in high-risk screening with no personal history of breast cancer. METHODS: Non-mutation carriers participating in the High-Risk Ontario Breast Screening Program at two sites were mailed demographic surveys, psychological scales, and chart review consent. Scales included the Consequences of Screening in Breast Cancer questionnaire, Lerman Breast Cancer Worry Scale, and Worry Interference Scale. Missing data were managed with multiple imputation. Multivariable regression was used to assess whether abnormal screens or biopsies were associated with adverse psychological effects. RESULTS: After contacting 465 participants, 169 non-mutation carriers were included. Median age was 46 years (range 30-65). Over a median 3 years of screening, 63.9% of women experienced at least one abnormal screen, and 24.9% underwent biopsies. Statements relating to cancer worry/anxiety scored highest, with 19.5% indicating they worried "a lot". Higher scores among anxiety-related statements were strongly associated with higher dejection scores. Overall, coping and daily functioning were preserved. Women indicated some positive reactions to screening, including improved existential values and reassurance they do not have breast cancer. Abnormal screens and biopsies were not significantly associated with any psychological scale, even after adjustment for patient characteristics. CONCLUSION: Non-mutation carriers undergoing MRI-based screening had considerable baseline anxiety and cancer worry, although daily functioning was not impaired. Abnormal screens and biopsies did not appear to have adverse psychological effects.

Methacholine-Induced Cough in the Absence of Asthma: Insights From Impulse Oscillometry.

INTRODUCTION: The pathophysiologic differences between methacholine-induced cough but normal airway sensitivity (COUGH) and healthy individuals (CONTROL) are incompletely understood and may be due to differences in the bronchodilating effect of deep inspirations (DIs). The purpose of this study is to compare the bronchodilating effect of DIs in individuals with classic asthma (CA), cough variant asthma (CVA), and COUGH with CONTROL and to assess impulse oscillometry (IOS) measures as predictors of the bronchodilating effect of DIs. METHODS: A total of 43 adults [18 female; 44.8 ± 12.3 years (mean ± SD); n = 11 CA, n = 10 CVA, n = 7 COUGH, n = 15 CONTROL] underwent modified high-dose methacholine challenge, with IOS and partial/maximal expiratory flow volume (PEFV/MEFV) maneuvers (used to calculate DI Index) to a maximum change (Δ) in FEV1 of 50% from baseline (MAX). Cough count and dyspnea were measured at each dose. The relation between IOS parameters and DI Index was assessed at baseline and MAX using multivariable linear regression analysis. RESULTS: Cough frequency, dyspnea intensity, and baseline peripheral resistance (R5-R20) were significantly greater in COUGH compared with CONTROL (p = 0.006, p = 0.029, and p = 0.035, respectively). At MAX, the DI Index was significantly lower in COUGH (0.01 ± 0.36) compared with CA (0.67 ± 0.97, p = 0.008), CVA (0.51 ± 0.73, p = 0.012), and CONTROL (0.68 ± 0.45, p = 0.005). Fres and R5-R20 were independent IOS predictors of the DI Index. CONCLUSION: The bronchodilating effect is impaired in COUGH and preserved in mild CA, CVA, and CONTROL. Increased peripheral airway resistance and decreased resonant frequency are associated with a decreased DI Index. COUGH is a clinical phenotype distinct from healthy normals and asthma.

Small-airway obstruction, dynamic hyperinflation, and gas trapping despite normal airway sensitivity to methacholine in adults with chronic cough.

The clinical relevance of cough during methacholine challenge in individuals with normal airway sensitivity is unknown. We compared responses of individuals with chronic cough who cough during high-dose methacholine bronchoprovocation and have normal versus increased airway sensitivity to healthy controls. Fifteen healthy participants (CONTROL) aged 26 ± 7 yr (mean ± SD) and 32 participants aged 42 ± 14 yr with chronic cough and suspected asthma completed high-dose methacholine challenge testing. Three participants who did not cough and had normal airway sensitivity were excluded. Spirometry and lung volumes were compared at the maximum response (MAX) among 1) ASTHMA [ n = 15, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (FEV1) from baseline (PC20) 4.71 ± 1.37 mg/ml], 2) methacholine-induced cough with normal airway sensitivity (COUGH, n = 14, PC20 41.2 ± 18.7 mg/ml for 3 participants with a measurable PC20), and 3) CONTROL ( n = 15; PC20 93.4 ± 95.4 mg/ml for 4 participants with a measurable PC20). Esophageal pressure-derived pulmonary mechanics were compared at MAX for the ASTHMA and COUGH groups. From baseline to MAX, FEV1 and forced expiratory flow between 25% and 75% of forced vital capacity decreased more in ASTHMA (-36.2 ± 3.8 %pr; -47.1 ± 6.9 %pr, respectively) than COUGH (-12.2 ± 3.0 %pr ( P < 0.001); -24.7 ± 6.5 %pr ( P < 0.001), respectively) and CONTROL (-13.7 ± 2.0 %pr ( P < 0.001); -32.8 ± 5.4 %pr ( P < 0.017), respectively). In both ASTHMA and COUGH, inspiratory capacity decreased by 500-800 ml, and functional residual capacity and residual volume increased by ~800 ml. Individuals with COUGH develop dynamic hyperinflation and gas trapping comparable to individuals with ASTHMA despite less bronchoconstriction and smaller reductions in mid-to-late expiratory flows, which leads us to believe that COUGH is a distinct phenotype. NEW & NOTEWORTHY Healthy individuals and individuals with chronic cough who demonstrate normal airway sensitivity but cough during methacholine bronchoprovocation bronchoconstrict less than individuals with mild asthma. However, those who cough and have normal airway sensitivity develop dynamic hyperinflation and gas trapping comparable to individuals with mild asthma. Thus, methacholine-induced cough with normal airway sensitivity may be clinically relevant, related to reversible small airway obstruction and preservation of the bronchodilating and/or bronchoprotective effects of deep inspirations.

Bronchoprotective effect of deep inspirations in cough variant asthma: A distinguishing feature in the spectrum of airway disease?

PURPOSE: To assess the effect of deep inspirations (DIs) on airway behaviour in individuals with classic asthma (CA), cough variant asthma (CVA), and methacholine (MCh)-induced cough but normal airway sensitivity (COUGH) during bronchoprovocation. METHODS: Twenty-five adults (18 female; 44.8 ±â€¯12.3 years (Mean ±â€¯SD); n = 9 CA, n = 9 CVA, and n = 7 COUGH) completed two single-dose MCh challenges, with and without DIs. Bronchoprotection was assessed by comparing changes in bronchoconstriction (FEV1, FVC, FEV1/FVC, FEF50, FEF25-75), gas trapping (RV, RV/TLC) and impulse oscillometry (IOS) measurements. RESULTS: The% changes in FEV1 with and without DIs were not significantly different within any group. Decreases in FEF50 and FEF25-75 were greater in CA (p = 0.041 and p = 0.029), decreases in FVC (% predicted) and FEV1/FVC(%) were less in CVA (p = 0.048 and p = 0.010), and increases in RV (L) and RV/TLC (% predicted) were less in COUGH (p = 0.007 and p = 0.028), respectively. No differences in IOS measurements were noted. CONCLUSIONS: DIs triggered bronchoconstriction in CA, bronchoprotection in CVA, and prevented gas trapping in COUGH.

Use of SNOMED CT® and LOINC® to standardize terminology for primary care asthma electronic health records.

OBJECTIVES: The burden of asthma ranks among the highest for chronic diseases. Interoperable electronic health records (EHRs) can improve the management of chronic diseases such as asthma by facilitating sharing of data between health care settings along the continuum of care. Terminology such as SNOMED CT® (Systematized Nomenclature of Medicine-Clinical Terms) and LOINC® (Logistical Observation Identifier Names and Codes) are prerequisites for interoperability of EHRs. We sought to determine the extent to which data elements in a validated asthma care map (ACM) are congruent with these terminologies. METHODS: A certified asthma educator entered all 169 elements in the ACM into the SNOMED CT® browser. Matched elements were assigned a concept name, an identification number, and classified into a hierarchy. LOINC® terminology was reviewed for asthma-related pulmonary function tests (PFTs). RESULTS: Forty-two percent of the ACM elements were complete matches to existing SNOMED CT® concepts, 24% partial matches, and 34% unmatched. Specific asthma control parameters were either complete (n = 3) or partial (n = 4) matches, but overall "asthma control" was unmatched. There were 92% complete or partial matches for PFT elements to SNOMED CT® and 83% to LOINC®. Conclusions: The majority of ACM elements are congruent with standardized terminology, enabling EHR interoperability. Future requests for new concepts in SNOMED CT® and LOINC® should be pursued for asthma control parameters paramount to evidence-based practice.

Assessing the burden of childhood asthma: validation of electronic versions of the Mini Pediatric and Pediatric Asthma Caregiver's Quality of Life Questionnaires.

PURPOSE: To validate electronic versions of the Mini Pediatric and Pediatric Asthma Caregiver's Quality of Life Questionnaires (MiniPAQLQ and PACQLQ, respectively), determine completion times and correlate QOL of children and caregivers. METHODS: A total of 63 children and 64 caregivers completed the paper and electronic MiniPAQLQ or PACQLQ. Agreement between versions of each questionnaire was summarized by intraclass correlation coefficients (ICC). The correlation between MiniPAQLQ and PACQLQ scores from child-caregiver pairs was assessed using Pearson's correlation coefficient. RESULTS: There was no significant difference (mean difference = 0.1, 95% CI -0.1, 0.2) in MiniPAQLQ Overall Scores between paper (5.9 ± 1.0, mean ± SD) and electronic (5.8 ± 1.0) versions, or any of the domains. ICCs ranged from 0.89 (Overall) to 0.86 (Emotional Function). Overall PACQLQ scores for both versions were comparable (5.9 ± 0.9 and 5.8 ± 1.0; mean difference = 0.0; 95% CI -0.1, 0.2). ICCs ranged from 0.81 (Activity Limitation) to 0.88 (Emotional Function). The electronic PACQLQ took 26 s longer (95% CI 11, 41; p < 0.001). Few participants (3-11%) preferred the paper format. MiniPAQLQ and PACQLQ scores were significantly correlated (all p < 0.05) for Overall (r paper = 0.33, r electronic = 0.27) and Emotional Function domains (r paper = 0.34, r electronic = 0.29). CONCLUSIONS: These electronic QOL questionnaires are valid, and asthma-related QOL of children and caregivers is related.

Changing face of ß2-adrenergic and muscarinic receptor therapies in asthma.

Despite current available treatment options, a significant proportion of patients with asthma remain uncontrolled and asthma pharmacotherapy continues to evolve. ß2-Adrenergic receptor agonists play a major role as bronchodilators in asthma therapy, although new perspectives reflect the potential for bias G-protein coupled receptor signaling pathways. Due to the success of muscarinic antagonists in chronic obstructive pulmonary disease, and the elucidation that muscarinic receptors play a role in airway remodeling, muscarinic receptors represent an attractive therapeutic target in asthma. Although short-acting muscarinic antagonists are currently limited to their use in acute asthma and as alternative bronchodilators in individuals who experience side effects with ß2-agonists, recent clinical trials indicate that the long-acting muscarinic antagonist, tiotropium, deserves consideration as a potential therapeutic agent for select populations. The continued evolution of anticholinergic therapy in asthma will require appropriately designed studies to assess mechanisms, efficacy and safety in asthma.