Impact of Treatable Traits on Asthma Control and Quality of Life.

BACKGROUND: Many adult patients with asthma have uncontrolled disease and impaired quality of life, despite current asthma-specific drug therapies. OBJECTIVE: This study aimed to investigate the prevalence of 9 traits in patients with asthma, their associations with disease control and quality of life, and referral rates to nonmedical health care professionals. METHODS: Retrospectively, data from patients with asthma were collected in 2 Dutch hospitals (Amphia Breda and RadboudUMC Nijmegen). Adult patients without exacerbation <3 months who were referred for a first-ever elective, outpatient, hospital-based diagnostic pathway were deemed eligible. Nine traits were assessed: dyspnea, fatigue, depression, overweight, exercise intolerance, physical inactivity, smoking, hyperventilation, and frequent exacerbations. To assess the likelihood of having poor disease control or decreased quality of life, the odds ratio (OR) was calculated per trait. Referral rates were assessed by checking patients' files. RESULTS: A total of 444 adults with asthma were studied (57% women, age: 48 ± 16 years, forced expiratory volume in 1 second: 88% ± 17% predicted). Most patients (53%) were found to have uncontrolled asthma (Asthma Control Questionnaire ≥1.5 points) and decreased quality of life (Asthma Quality of Life Questionnaire <6 points). Generally, patients had 3.0 ± 1.8 traits. Severe fatigue was most prevalent (60%) and significantly increased the likelihood of having uncontrolled asthma (OR: 3.0, 95% confidence interval [CI]: 1.9-4.7) and decreased quality of life (OR: 4.6, 95% CI: 2.7-7.9). Referrals to nonmedical health care professionals were low; most referrals were to a respiratory-specialized nurse (33%). CONCLUSION: Adult patients with asthma with a first-ever referral to a pulmonologist frequently exhibit traits justifying the deployment of nonpharmacological interventions, especially in those with uncontrolled asthma. However, referrals to appropriate interventions appeared infrequent.

Patient activation is a treatable trait in patients with chronic airway diseases: An observational study.

Background: Self-management is key for reducing the burden of disease in chronical illness. However, applying self-management presupposes behavioral change. Sufficient knowledge, skills, confidence and motivation to make the needed behavior changes are important prerequisites. During the past years the Integral Diagnostic Trajectory was developed for patients with asthma or COPD which aims to identify treatable traits and activating patients for self-management. Objective: In the present study the effects of the Integral Diagnostic Trajectory on the Patient Activation Measure (PAM®) were examined. In addition, predictive variables for PAM baseline scores and change scores were sought. Materials and methods: A total of 241 patients with asthma or COPD referred to the pulmonologist at the Radboud university medical center, location Dekkerswald, Nijmegen were included. Patient activation was measured before the first visit and after the intervention with the 13-item PAM®. Additional, patient characteristics and health status were measured with the Nijmegen Clinical Screening Instrument (NCSI), modified Medical Research Council (mMRC), Asthma Control Questionnaire (ACQ), and COPD Clinical Questionnaire (CCQ). Results: Fifty percent of the patients with asthma and seventy percent of the patients with COPD had low levels of activation at baseline (PAM level 1-2). Baseline PAM scores could be explained in patients with asthma for 7% by number of severe problems in health status. And for 18% in patients with COPD by number of severe problems, age and employment status. After the intervention both groups significantly improved on the PAM (T0: 56.0 ± 13.1 vs. T1:63.3 ± 14.0 in asthma, and T0: 50.0 ± 8.8 vs. 58.4 ± 11.1 in COPD). Multivariate stepwise regression analysis showed that only 24% of the change in score could be explained by baseline PAM score and being employed in patients with asthma, and 18% of the variance in change score could be predicted by baseline PAM score in COPD. Conclusion: The present study showed that low level of activation is a common feature in patients with asthma and COPD. With a relatively short and seemingly simple intervention patients can reach higher levels of patient activation, which is a prerequisite for adopting self-management techniques in daily life.

Differences in Pulmonary and Extra-Pulmonary Traits between Women and Men with Chronic Obstructive Pulmonary Disease.

Background: Evidence suggests sex-related differences in chronic obstructive pulmonary disease (COPD). Whether these differences are reflected in the prevalence of treatable traits remains unknown. Methods: Two samples of patients referred to secondary (n = 530) or tertiary care (n = 2012) were analyzed. Men and women were matched for age, forced expiratory volume in 1 s and body mass index. Sex-related differences were tested using t-tests, Mann-Whitney U, or chi-square tests. Results: Frequent exacerbations (30.5 vs. 19.7%), high cardiovascular risk (88.1 vs. 66.2%) and activity-related severe dyspnea (50.9 vs. 34.8%) were more prevalent in women in secondary care (p < 0.05). Severe hyperinflation (43.0 vs. 25.4%), limited diffusing capacity (79.6 vs. 70.1%), impaired mobility (44.0 vs. 28.7%), frequent exacerbations (66.8 vs. 57.4%), frequent hospitalizations (47.5 vs. 41.6%), severe activity-related dyspnea (89.1 vs. 85.0%), symptoms of anxiety (56.3 vs. 42.0%) and depression (50.3 vs. 44.8%), and poor health status (79.9 vs. 71.0%) were more prevalent in women in tertiary care (p < 0.05). Severe inspiratory muscle weakness (14.6 vs. 8.2%) and impaired exercise capacity (69.1 vs. 59.6%) were more prevalent among men (p < 0.05) in tertiary care. Conclusions: Sex-related differences were found, with most traits more prevalent and severe among women. Care providers should be aware of these differences to adjust treatment.

"Can Do, Do Do" Quadrants and 6-Year All-Cause Mortality in Patients With COPD.

BACKGROUND: Physical capacity (PC; "can do") and physical activity (PA; "do do") are prognostic indicators in COPD and can be used to subdivide patients with COPD into four exclusive subgroups (the so-called "can do, do do" quadrants). This concept may be useful to understand better the impact of PC and PA on all-cause mortality in patients with COPD. RESEARCH QUESTION: What is the 6-year all-cause mortality risk of the "can do, do do" quadrants of patients with COPD? STUDY DESIGN AND METHODS: This retrospective study used data from patients with COPD who underwent a comprehensive assessment at their first-ever outpatient consultation. PC was assessed using the 6-min walk distance and physical activity was assessed using an accelerometer (steps per day). All-cause mortality data were obtained from the Municipal Personal Records Database. Receiver operating characteristic curves were used to determine threshold values for PC and PA to predict 6-year all-cause mortality. Using the derived threshold values, male and female patients were divided into the four "can do, do do" quadrants. RESULTS: Data from 829 patients were used for analyses. Best discriminatory values for 6-year mortality were 404 m and 4,125 steps/day for men and 394 m and 4,005 steps/day for women. During a median follow-up of 55 months (interquartile range, 37-71 months), 129 patients (15.6%) died. After controlling for established prognostic factors, patients in the "can do, don't do" quadrant and "can do, do do" quadrant showed significantly lower mortality risk compared with patients in the "can't do, don't do" quadrant: hazard ratios of 0.36 (95% CI, 0.14-0.93) and 0.24 (95% CI, 0.09-0.61) for men and 0.37 (95% CI, 0.38-0.99) and 0.29 (95% CI, 0.10-0.87) for women, respectively. No significant differences were found between the "can't do, do do" and "can't do, don't do" quadrants. INTERPRETATION: Patients with COPD with a preserved PC seem to have a significantly lower 6-year mortality risk compared with patients with a decreased PC, regardless of physical activity level.

Prevalence of hyperventilation in patients with asthma.

OBJECTIVE: Asthma is frequently accompanied by dysfunctional breathing of which hyperventilation has been recognized as a subtype. The prevalence of hyperventilation in stable asthma has been scantily studied using blood gas analysis. Hence, a reliable estimate of its prevalence is lacking. It is unknown whether the Nijmegen Questionnaire (NQ) is a useful screening tool for hyperventilation in asthma. Therefore, the primary aim of this study was to determine the prevalence of hyperventilation in a large sample of patients with asthma in a stable state of disease. Secondary aims were to compare the clinical characteristics between patients with and without hyperventilation, and, to examine the concurrent validity of the NQ to detect hypocapnia in patients with asthma. METHODS: A real-world, observational, multicenter study was conducted. Capillary blood gas analysis was performed in adults with a confirmed diagnosis of stable asthma. A subset of patients completed the NQ. RESULTS: A blood gas analysis was obtained in 1006 patients. In 17% of the patients an acute hyperventilation was found, and in another 23% a chronic hyperventilation was uncovered. Patients with a chronic hyperventilation blood gas were more often female, were younger and had a better spirometric outcomes. The NQ appeared not to correlate with PCO2. CONCLUSION: Hyperventilation is common in patients with stable asthma. Chronic hyperventilation is more often found in females of younger age and with the best spirometric outcomes compared to patients without hyperventilation. The NQ is not a suitable screening tool for the presence of hyperventilation in stable asthmatics.

Characteristics and treatable traits of patients with chronic obstructive pulmonary disease (COPD) with and without paid employment.

INTRODUCTION: Patients with COPD are vulnerable to workforce detachment. Better knowledge of features associated with paid work loss might be of help to design and select appropriate interventions. METHOD: This cross-sectional study aimed to explore the presence of treatable traits in COPD patients without paid work. Patients with COPD below 65 years at first referral to a hospital-based patient clinic were included. Using binary logistic regression analysis, the relationship between paid work and the following characteristics was explored: low daily physical activity, exercise, active smoking, Medical Research Council dyspnea scale (MRC), poor nutritional status, exacerbations, and fatigue (checklist individual strength (CIS)). Variables were adjusted for age, sex, forced expiratory volume in 1 s (FEV 1), and education level. RESULTS: In total, 191 patients (47.3%) were without paid work. The following treatable traits were related to not being in paid work: < 5000 steps/day (OR 2.36, 95% CI (1.52-3.68)), MRC ≥ 3 (OR 1.78, 95%CI (1.14-2.77)), CIS ≥ 36 points (OR 1.78, 95% CI (1.10-2.87)), six-minute walk distance (6MWD) < 70% of predicted (OR 2.62, 95% CI (1.69-4.06)), and ≥ 2 exacerbations per year (OR 1.80, 95% CI (1.12-2.92)). Significant differences were also seen in age (OR 1.06, 95% CI (1.02-1.10) per year), FEV 1% predicted (OR 0.98, 95% CI (0.97-1.00) per % predicted increase), and medium/high education level (OR 0.62, 95% CI (0.41-0.93)). When adjusting for all variables the only treatable trait that remained significant was 6MWD. CONCLUSION: Patients without paid work are more likely to have treatable traits with 6MWD revealing the most significant association.

Effectiveness of Home-Based Occupational Therapy on COPM Performance and Satisfaction Scores in Patients with COPD.

BACKGROUND.: Occupational therapy (OT) may be an important intervention in patients with COPD, but studies show conflicting results. PURPOSE.: To evaluate the effectiveness of home-based monodisciplinary OT in COPD patients. METHOD.: We conducted an observational clinical study. Main outcomes were the mean differences in the Canadian Occupational Performance Measure (COPM) performance and satisfaction scores, pre and post intervention. FINDINGS.: Pre- and postintervention data were obtained from 41 patients. Statistically significant increases were observed in COPM performance (5.0 ± 1.1 versus 6.9 ± 0.9; P<0.001) and satisfaction (4.6 ± 1.3 versus 6.9 ± 1.0; P<0.001). The most frequently reported occupational performance problems were found in the domains of productivity (47%) and mobility (40%), fewer in self-care (10%) and the least in leisure (3%). IMPLICATIONS.: Home-based monodisciplinary OT can contribute significantly to the improvement of daily functioning of patients with COPD. OT should therefore be considered more often as part of the integrated management of these patients.

"Can Do" Versus "Do Do" in Patients with Asthma at First Referral to a Pulmonologist.

BACKGROUND: Pharmacotherapy is key in asthma control, including preventing lung function decline, in primary care. However, patients' physical functioning (eg, physical capacity [PC] [=can do] and physical activity [PA] [=do do]) correlates poorly with lung function. Therefore, a better insight into the physical function of patients with asthma is needed, using the "can do, do do" concept. OBJECTIVE: To explore the "can do, do do" concept in adult patients with asthma at referral for the first time to an outpatient consultation of a pulmonologist. METHODS: PC was measured using the six-minute walk test and PA by using an accelerometer. Patients were classified into quadrants: low PC (6-minute walking distance <70% predicted), low PA (<7000 steps/d, "'can't do, don't do"); preserved PC, low PA ("can do, don't do"); low PC, preserved PA ("'can't do, do do"); or preserved PC, preserved PA ("can do, do do"). RESULTS: A total of 479 patients with asthma had a median (interquartile range) 6-minute walking distance of 74% (66%-82%) predicted, and walked 6829 (4593-9075) steps/d. Only 29% were classified as "can do, do do," whereas 30% were classified as "can't do, don't do." The Asthma Control Questionnaire and the Asthma Quality of Life Questionnaire scores were worst in the "can't do" groups. CONCLUSIONS: Low PC and/or PA was found in most patients with asthma at the index referral to a pulmonologist. An impaired PC is accompanied by a significantly reduced asthma control and disease-specific quality of life. This justifies further studies on safety and efficacy of nonpharmacological interventions, such as physiotherapy.

Treatable traits qualifying for nonpharmacological interventions in COPD patients upon first referral to a pulmonologist: the COPD sTRAITosphere.

INTRODUCTION: The present study assessed the prevalence of nine treatable traits (TTs) pinpointing nonpharmacological interventions in patients with COPD upon first referral to a pulmonologist, how these TTs co-occurred and whether and to what extent the TTs increased the odds having a severely impaired health status. METHODS: Data were collected from a sample of 402 COPD patients. A second sample of 381 patients with COPD was used for validation. Nine TTs were assessed: current smoking status, activity-related dyspnoea, frequent exacerbations <12 months, severe fatigue, depressed mood, poor physical capacity, low physical activity, poor nutritional status and a low level of self-management activation. For each TT the odds ratio (OR) of having a severe health status impairment was calculated. Furthermore, a graphic representation was created, the COPD sTRAITosphere, to visualise TTs prevalence and OR. RESULTS: On average 3.9±2.0 TTs per patient were observed. These TTs occurred relatively independently of each other and coexisted in 151 unique combinations. A significant positive correlation was found between the number of TTs and Clinical COPD Questionnaire total score (r=0.58; p<0.001). Patients with severe fatigue (OR: 8.8), severe activity-related dyspnoea (OR: 5.8) or depressed mood (OR: 4.2) had the highest likelihood of having a severely impaired health status. The validation sample corroborated these findings. CONCLUSIONS: Upon first referral to a pulmonologist, COPD patients show multiple TTs indicating them to several nonpharmacological interventions. These TTs coexist in many different combinations, are relatively independent and increase the likelihood of having a severely impaired health status.

Profiling of Patients with COPD for Adequate Referral to Exercise-Based Care: The Dutch Model.

A loss of physical functioning (i.e., a low physical capacity and/or a low physical activity) is a common feature in patients with chronic obstructive pulmonary disease (COPD). To date, the primary care physiotherapy and specialized pulmonary rehabilitation are clearly underused, and limited to patients with a moderate to very severe degree of airflow limitation (GOLD stage 2 or higher). However, improved referral rates are a necessity to lower the burden for patients with COPD and for society. Therefore, a multidisciplinary group of healthcare professionals and scientists proposes a new model for referral of patients with COPD to the right type of exercise-based care, irrespective of the degree of airflow limitation. Indeed, disease instability (recent hospitalization, yes/no), the burden of disease (no/low, mild/moderate or high), physical capacity (low or preserved) and physical activity (low or preserved) need to be used to allocate patients to one of the six distinct patient profiles. Patients with profile 1 or 2 will not be referred for physiotherapy; patients with profiles 3-5 will be referred for primary care physiotherapy; and patients with profile 6 will be referred for screening for specialized pulmonary rehabilitation. The proposed Dutch model has the intention to get the right patient with COPD allocated to the right type of exercise-based care and at the right moment.

Pulmonary Rehabilitation Reduces Subjective Fatigue in COPD: A Responder Analysis.

To date, it remains unknown which patients report a clinically-relevant improvement in fatigue following pulmonary rehabilitation (PR). The purpose of this study was to identify and characterize these responders. Demographics, lung function, anxiety (anxiety subscale of the 90-item symptom checklist (SCL-90-A)), depression (Beck depression inventory for primary care (BDI-PC)), exercise tolerance (six-minute walking distance test (6MWD)), and health status (Nijmegen clinical screening instrument (NCSI)) were assessed before and after a 12-week PR programme. Fatigue was assessed using the checklist individual strength (CIS)-Fatigue. Patients with a decline ≥ 10 points (minimally clinically important difference, MCID) on the CIS-Fatigue were defined as responders. Chronic obstructive pulmonary disease (COPD) patients (n = 446, 61 ± 9 years, 53% male, forced expiratory volume in 1 s (FEV1) 43% ± 18% predicted, 75% severe fatigue) were included. Mean change in fatigue after PR was 10 ± 12 points (p < 0.01) and exceeded the MCID. In total, 56% were identified as fatigue responders. Baseline CIS-Fatigue (45 ± 7 vs. 38 ± 9 points, respectively, p < 0.001) and health-related quality-of-life (HRQoL; p < 0.001) were different between responders and non-responders. No differences were found in demographics, baseline anxiety, depression, lung function, 6MWD, and dyspnoea (p-values > 0.01). Responders on fatigue reported a greater improvement in anxiety, depression, 6MWD, dyspnoea (all p-values < 0.001), and most health status parameters. PR reduces fatigue in COPD. Responders on fatigue have worse fatigue and HRQoL scores at baseline, and are also likely to be responders on other outcomes of PR.

Fatigue is Highly Prevalent in Patients with Asthma and Contributes to the Burden of Disease.

The 2018 update of the Global Strategy for Asthma Management and Prevention does not mention fatigue-related symptoms. Nevertheless, patients with asthma frequently report tiredness, lack of energy, and daytime sleepiness. Quantitative research regarding the prevalence of fatigue in asthmatic patients is lacking. This retrospective cross-sectional study of outpatients with asthma upon referral to a chest physician assessed fatigue (Checklist Individual Strength-Fatigue (CIS-Fatigue)), lung function (spirometry), asthma control (Asthma Control Questionnaire (ACQ)), dyspnea (Medical Research Council (MRC) scale), exercise capacity (six-minute walk test (6MWT)), and asthma-related Quality-of-Life (QoL), Asthma Quality of Life Questionnaire (AQLQ) during a comprehensive health-status assessment. In total, 733 asthmatic patients were eligible and analyzed (47.4 ± 16.3 years, 41.1% male). Severe fatigue (CIS-Fatigue ≥ 36 points) was detected in 62.6% of patients. Fatigue was not related to airflow limitation (FEV1, ρ = -0.083); was related moderately to ACQ (ρ = 0.455), AQLQ (ρ = -0.554), and MRC (ρ = 0.435; all p-values < 0.001); and was related weakly to 6MWT (ρ = -0.243, p < 0.001). In stepwise multiple regression analysis, 28.9% of variance in fatigue was explained by ACQ (21.0%), MRC (6.5%), and age (1.4%). As for AQLQ, 42.2% of variance was explained by fatigue (29.8%), MRC (8.6%), exacerbation rate (2.6%), and age (1.2%). Severe fatigue is highly prevalent in asthmatic patients; it is an important determinant of disease-specific QoL and a crucial yet ignored patient-related outcome in patients with asthma.

Double-stranded RNA-exposed human keratinocytes promote Th1 responses by inducing a Type-1 polarized phenotype in dendritic cells: role of keratinocyte-derived tumor necrosis factor alpha, type I interferons, and interleukin-18.

Dendritic cells play a key role in establishing the class of immune response against invading pathogens. Upon engagement with double-stranded RNA, a major bioactive constituent of many virus types, immature dendritic cells develop into type 1 immunostimulatory dendritic cells that promote Th1 responses. Immature dendritic cells reside in the epithelia and are in close contact with keratinocytes. We studied to what extent dendritic cells can also adopt a type 1 immunostimulatory dendritic cell phenotype indirectly, as a result of the interaction with keratinocytes responding to double-stranded RNA. In contrast to supernatants from keratinocytes activated by the combination of tumor necrosis factor alpha and interleukin-1beta, supernatants from keratinocytes activated by synthetic double-stranded RNA, polyriboinosinic polyribocytidylic acid, comprised tumor necrosis factor alpha and type I interferons, which induced maturation of human monocyte-derived immature dendritic cells. In addition, dendritic cells matured in the presence of these supernatants strongly biased the development of Th1 cells from naive Th cells. This bias was dependent on keratinocyte-derived interferon-alpha/beta and interleukin-18, as neutralization of both interferon-alpha/beta and interleukin-18 in the keratinocyte culture supernatant reduced the development of interferon-gamma-producing Th cells. These findings suggest that keratinocytes can contribute to the development of selective Th1/Th2 responses through the induction of maturation and functional polarization of dendritic cells, indicating a novel role for keratinocytes as initiators and regulators of cutaneous T-cell-mediated inflammation. In addition, these results support the concept that, in addition to direct interaction with pathogens, dendritic cells may also be activated and primed by pathogen indirectly, via the effect of resident tissue cells responding to pathogen.