Clinical practice of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Non-invasive ventilation (NIV) is an evidence-based treatment for acute respiratory failure in chronic obstructive pulmonary disease (COPD). However, suboptimal application of NIV in clinical practice, possibly due to poor guideline adherence, can impact patient outcomes. This study aims to evaluate guideline adherence to NIV for acute COPD exacerbations and explore its impact on mortality. METHODS: This retrospective study was performed in two Dutch medical centers from 2019 to 2021. All patients admitted to the pulmonary ward or intensive care unit with a COPD exacerbation were included. An indication for NIV was considered in the event of a respiratory acidosis. RESULTS: A total of 1162 admissions (668 unique patients) were included. NIV was started in 154 of the 204 admissions (76%) where NIV was indicated upon admission. Among 78 admissions where patients deteriorated later on, NIV was started in 51 admissions (65%). Considering patients not receiving NIV due to contra-indications or patient refusal, the overall guideline adherence rate was 82%. Common reasons for not starting NIV when indicated included no perceived signs of respiratory distress, opting for comfort care only, and choosing a watchful waiting approach. Better survival was observed in patients who received NIV when indicated compared to those who did not. CONCLUSIONS: The adherence to guidelines regarding NIV initiation is good. Nevertheless, further improving NIV treatment in clinical practice could be achieved through training healthcare professionals to increase awareness and reduce reluctance in utilizing NIV. By addressing these factors, patient outcomes may be further enhanced.

Sleep Hypoventilation is Common in Diurnal Normocapnic COPD Patients with Severe or Very Severe Obstruction and is Not Associated with Body Mass Index.

Sleep hypoventilation (SH) is common in COPD patients with diurnal hypercapnia, however there are little data on the presence of SH in COPD patients with diurnal normocapnia. In this study the prevalence of SH in stable normocapnic COPD patients with severe or very severe obstruction (GOLD stages III and IV) was evaluated across body mass index (BMI) classes and associations between SH and body composition measures were explored. A total of 56 diurnal normocapnic COPD patients, of whom 17 normal-weight (COPDNW), 18 overweight (COPDOW) and 21 obese (COPDOB), underwent polysomnography to objectify SH and bioelectrical impedance analysis to assess body composition. The overall prevalence of SH was 66.1% and was not different across BMI classes. Logistic regression models indicated that SH was not associated with waist-to-hip ratio, body fat percentage and fat-free mass index. Our data indicate that SH is common in diurnal normocapnic COPD patients with severe or very severe obstruction and is not associated with BMI or body composition.

Early rheumatoid arthritis treated with tocilizumab, methotrexate, or their combination (U-Act-Early): a multicentre, randomised, double-blind, double-dummy, strategy trial.

BACKGROUND: For patients with newly diagnosed rheumatoid arthritis, treatment aim is early, rapid, and sustained remission. We compared the efficacy and safety of strategies initiating the interleukin-6 receptor-blocking monoclonal antibody tocilizumab with or without methotrexate (a conventional synthetic disease-modifying antirheumatic drug [DMARD]), versus initiation of methotrexate monotherapy in line with international guidelines. METHODS: We did a 2-year, multicentre, randomised, double-blind, double-dummy, strategy study at 21 rheumatology outpatient departments in the Netherlands. We included patients who had been diagnosed with rheumatoid arthritis within 1 year before inclusion, were DMARD-naive, aged 18 years or older, met current rheumatoid arthritis classification criteria, and had a disease activity score assessing 28 joints (DAS28) of at least 2·6. We randomly assigned patients (1:1:1) to start tocilizumab plus methotrexate (the tocilizumab plus methotrexate arm), or tocilizumab plus placebo-methotrexate (the tocilizumab arm), or methotrexate plus placebo-tocilizumab (the methotrexate arm). Tocilizumab was given at 8 mg/kg intravenously every 4 weeks with a maximum of 800 mg per dose. Methotrexate was started at 10 mg per week orally and increased stepwise every 4 weeks by 5 mg to a maximum of 30 mg per week, until remission or dose-limiting toxicity. We did the randomisation using an interactive web response system. Masking was achieved with placebos that were similar in appearance to the active drug; the study physicians, pharmacists, monitors, and patients remained masked during the study, and all assessments were done by masked assessors. Patients not achieving remission on their initial regimen switched from placebo to active treatments; patients in the tocilizumab plus methotrexate arm switched to standard of care therapy (typically methotrexate combined with a tumour necrosis factor inhibitor). When sustained remission was achieved, methotrexate (and placebo-methotrexate) was tapered and stopped, then tocilizumab (and placebo-tocilizumab) was also tapered and stopped. The primary endpoint was the proportion of patients achieving sustained remission (defined as DAS28 <2·6 with a swollen joint count ≤four, persisting for at least 24 weeks) on the initial regimen and during the entire study duration, compared between groups with a two-sided Cochran-Mantel-Haenszel test. Analysis was based on an intention-to-treat method. This trial was registered at ClinicalTrials.gov, number NCT01034137. FINDINGS: Between Jan 13, 2010, and July 30, 2012, we recruited and assigned 317 eligible patients to treatment (106 to the tocilizumab plus methotrexate arm, 103 to the tocilizumab arm, and 108 to the methotrexate arm). The study was completed by a similar proportion of patients in the three groups (range 72-78%). The most frequent reasons for dropout were adverse events or intercurrent illness: 27 (34%) of dropouts, and insufficient response: 26 (33%) of dropouts. 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm achieved sustained remission on the initial regimen, compared with 86 (84%) of 103 in the tocilizumab arm, and 48 (44%) of 108 in the methotrexate arm (relative risk [RR] 2·00, 95% CI 1·59-2·51 for tocilizumab plus methotrexate vs methotrexate, and 1·86, 1·48-2·32 for tocilizumab vs methotrexate, p<0·0001 for both comparisons). For the entire study, 91 (86%) of 106 patients in the tocilizumab plus methotrexate arm, 91 (88%) of 103 in the tocilizumab arm, and 83 (77%) of 108 in the methotrexate arm achieved sustained remission (RR 1·13, 95% CI 1·00-1·29, p=0·06 for tocilizumab plus methotrexate vs methotrexate, 1·14, 1·01-1·29, p=0·0356 for tocilizumab vs methotrexate, and p=0·59 for tocilizumab plus methotrexate vs tocilizumab). Nasopharyngitis was the most common adverse event in all three treatment groups, occurring in 38 (36%) of 106 patients in the tocilizumab plus methotrexate arm, 40 (39%) of 103 in the tocilizumab arm, and 37 (34%) of 108 in the methotrexate arm. The occurrence of serious adverse events did not differ between the treatment groups (17 [16%] of 106 patients in the tocilizumab plus methotrexate arm vs 19 [18%] of 103 in the tocilizumab arm and 13 [12%] of 108 in the methotrexate arm), and no deaths occurred during the study. INTERPRETATION: For patients with newly diagnosed rheumatoid arthritis, strategies aimed at sustained remission by immediate initiation of tocilizumab with or without methotrexate are more effective, and with a similar safety profile, compared with initiation of methotrexate in line with current standards. FUNDING: Roche Nederland BV.

Manual vs. automated analysis of polysomnographic recordings in patients with chronic obstructive pulmonary disease.

PURPOSE: The sleep quality, as assessed by polysomnography (PSG), of patients with chronic obstructive pulmonary disease (COPD) can be severely disturbed. The manual analysis of PSGs is time-consuming, and computer systems have been developed to automatically analyze PSGs. Studies on the reliability of automated analyses in healthy subjects show varying results, and the purpose of this study was to assess whether automated analysis of PSG by one certain automatic system in patients with COPD provide accurate outcomes when compared to manual analysis. METHODS: In a retrospective study, the full-night polysomnographic recordings of patients with and without COPD were analyzed automatically by Matrix Sleep Analysis software and manually. The outcomes of manual and automated analyses in both groups were compared using Bland-Altman plots and Students' paired t tests. RESULTS: Fifty PSGs from patients with COPD and 57 PSGs from patients without COPD were included. In both study groups, agreement between manual and automated analysis was poor in nearly all sleep and respiratory parameters, like total sleep time, sleep efficiency, sleep latency, amount of rapid eye movement sleep and other sleep stages, number of arousals, apnea-hypopnea index, and desaturation index. CONCLUSION: Automated analysis of PSGs by the studied automated system in patients with COPD has poor agreement with manual analysis when looking at sleep and respiratory parameters and should, therefore, not replace the manual analysis of PSG recordings in patients with COPD.

Identification of Risk Factors for COVID-19 Hospitalization in Patients With Anti-Rheumatic Drugs: Results From a Multicenter Nested Case Control Study.

Patients with inflammatory rheumatic diseases (IRDs) do not have an increased risk for coronavirus disease 2019 (COVID-19) compared with the general population. However, it remains uncertain whether subgroups of patients with IRD using different immunosuppressive antirheumatic drugs carry a higher risk for severe COVID-19 compared with other patients with IRD. The aim of this study is to identify risk factors for severe COVID-19, requiring hospitalization in patients with IRD. This is a multicenter nested case control study conducted in the Netherlands. Cases are hospital known patients with IRD requiring hospitalization for COVID-19 between March 1, 2020, and May 31, 2020. Controls are hospital known patients with IRD not requiring hospitalization for COVID-19 in this period, included at a 4:1 ratio. Patient, disease, and treatment characteristics were extracted from electronic medical records and a questionnaire. Potential risk factors were analyzed using unconditional logistic regression, corrected for confounders and multiple testing. Eighty-one cases and 396 controls were included. General risk factors of older age and obesity apply to patients with IRD as well (odds ratio (OR) for age ≥ 75 3.5, 95% confidence interval (CI) 1.9-6.3, OR for body mass index ≥ 40 4.5, 95% CI 1.5-14). No significantly increased ORs for COVID-19 hospitalization were found for any antirheumatic agent or IRD. A protective effect was found for use of methotrexate (OR 0.53, 95% CI 0.31-0.92). In conclusion, similar to the general population, elderly and obese patients with IRD have a higher risk for hospitalization for COVID-19. We did not identify a specific antirheumatic agent or IRD to increase the risk of COVID-19 hospitalization in patients with IRD, except for a possible protective effect of methotrexate.

Effectiveness of a Mobile Health and Self-Management App for High-Risk Patients With Chronic Obstructive Pulmonary Disease in Daily Clinical Practice: Mixed Methods Evaluation Study.

BACKGROUND: Mobile health and self-management interventions may positively affect behavioral change and reduce hospital admissions for patients with chronic obstructive pulmonary disease (COPD). However, not all patients qualify for these interventions, and systematic, comprehensive information on implementation- and compliance-related aspects of mobile self-management apps is lacking. Due to the tendency to target digital services to patients in stable phases of disease, it is especially relevant to focus on the use of these services in broad clinical practice for patients recently discharged from hospital. OBJECTIVE: This study aims to evaluate the effects of a mobile health and self-management app in clinical practice for recently discharged patients with COPD on use of the app, self-management, expectations, and experiences (technology acceptance); patients' and nurses' satisfaction; and hospital readmissions. METHODS: A prototype of the app was pilot tested with 6 patients with COPD. The COPD app consisted of an 8-week program including the Lung Attack Action Plan, education, medication overview, video consultation, and questionnaires (monitored by nurses). In the feasibility study, adult patients with physician-diagnosed COPD, access to a mobile device, and proficiency of the Dutch language were included from a large teaching hospital during hospital admission. Self-management (Partners in Health Scale), technology acceptance (Unified Theory Acceptance and Use of Technology model), and satisfaction were assessed using questionnaires at baseline, after 8 weeks, and 20 weeks. Use was assessed with log data, and readmission rates were extracted from the electronic medical record. RESULTS: A total of 39 patients were included; 76.4% (133/174) of patients had to be excluded from participation, and 48.9% of those patients (65/133) were excluded because of lack of digital skills, access to a mobile device, or access to the internet. The COPD app was opened most often in the first week (median 6.0; IQR 3.5-10.0), but its use decreased over time. The self-management element knowledge and coping increased significantly over time (P=.04). The COPD app was rated on a scale of 1-10, with an average score by patients of 7.7 (SD 1.7) and by nurses of 6.3 (SD 1.2). Preliminary evidence about the readmission rate showed that 13% (5/39) of patients were readmitted within 30 days; 31% (12/39) of patients were readmitted within 20 weeks, compared with 14.1% (48/340) and 21.8% (74/340) in a preresearch cohort, respectively. CONCLUSIONS: The use of a mobile self-management app after hospital discharge seems to be feasible only for a small number of patients with COPD. Patients were satisfied with the service; however, use decreased over time, and only knowledge and coping changed significantly over time. Therefore, future research on digital self-management interventions in clinical practice should focus on including more difficult subgroups of target populations, a multidisciplinary approach, technology-related aspects (such as acceptability), and fine-tuning its adoption in clinical pathways. TRIAL REGISTRATION: Clinicaltrials.gov NCT04540562; https://clinicaltrials.gov/ct2/show/NCT04540562.

Video Consultation as an Adequate Alternative to Face-to-Face Consultation in Continuous Positive Airway Pressure Use for Newly Diagnosed Patients With Obstructive Sleep Apnea: Randomized Controlled Trial.

BACKGROUND: The effectiveness of continuous positive airway pressure (CPAP) is dependent on the degree of use, so adherence is essential. Cognitive components (eg, self-efficacy) and support during treatment have been found to be important in CPAP use. Video consultation may be useful to support patients during treatment. So far, video consultation has rarely been evaluated in thorough controlled research, with only a limited number of outcomes assessed. OBJECTIVE: The aim of the study was to evaluate the superiority of video consultation over face-to-face consultation for patients with obstructive sleep apnea (OSA) on CPAP use (minutes per night), adherence, self-efficacy, risk outcomes, outcome expectancies, expectations and experiences with video consultation, and satisfaction of patients and nurses. METHODS: A randomized controlled trial was conducted with an intervention (video consultation) and a usual care group (face-to-face consultation). Patients with confirmed OSA (apnea-hypopnea index >15), requiring CPAP treatment, no history of CPAP treatment, having access to a tablet or smartphone, and proficient in the Dutch language were recruited from a large teaching hospital. CPAP use was monitored remotely, with short-term (weeks 1 to 4) and long-term (week 4, week 12, and week 24) assessments. Questionnaires were completed at baseline and after 4 weeks on self-efficacy, risk perception, outcome expectancies (Self-Efficacy Measure for Sleep Apnea), expectations and experiences with video consultation (covering constructs of the unified theory of acceptance and use of technology), and satisfaction. Nurse satisfaction was evaluated using questionnaires. RESULTS: A total of 140 patients were randomized (1:1 allocation). The use of video consultation for OSA patients does not lead to superior results on CPAP use and adherence compared with face-to-face consultation. A significant difference in change over time was found between groups for short-term (P-interaction=.008) but not long-term (P-interaction=.68) CPAP use. CPAP use decreased in the long term (P=.008), but no significant difference was found between groups (P=.09). Change over time for adherence was not significantly different in the short term (P-interaction=.17) or long term (P-interaction=.51). A relation was found between CPAP use and self-efficacy (P=.001), regardless of the intervention arm (P=.25). No significant difference between groups was found for outcome expectancies (P=.64), self-efficacy (P=.41), and risk perception (P=.30). The experiences were positive, and 95% (60/63) intended to keep using video consultation. Patients in both groups rated the consultations on average with an 8.4. Overall, nurses (n=3) were satisfied with the video consultation system. CONCLUSIONS: Support of OSA patients with video consultation does not lead to superior results on CPAP use and adherence compared with face-to-face consultation. The findings of this research suggest that self-efficacy is an important factor in improving CPAP use and that video consultation may be a feasible way to support patients starting CPAP. Future research should focus on blended care approaches in which self-efficacy receives greater emphasis. TRIAL REGISTRATION: Clinicaltrials.gov NCT04563169; https://clinicaltrials.gov/show/NCT04563169.

Accuracy of transcutaneous carbon dioxide tension measurements during cardiopulmonary exercise testing.

BACKGROUND: Measurements of transcutaneous carbon dioxide tension (PtcCO(2)) with current devices are proven to provide clinically acceptable agreement with measurements of partial arterial carbon dioxide tension (PaCO(2)) in several settings but not during cardiopulmonary exercise testing (CPET). OBJECTIVES: The primary objective of this study was to investigate the agreement between PaCO(2) and PtcCO(2) measurements (using a Tosca 500 with a Tosca sensor 92) during CPET. A secondary objective was to investigate the agreement between arterial and transcutaneous oxygen saturation (SaO(2), SpO(2)) as measured with this sensor during CPET. METHODS: In patients with various pulmonary diseases, PtcCO(2) and SpO(2) were continuously measured and compared with arterial blood gas samples during CPET. A maximum bias of 0.5 kPa and 95% limits of agreement (LOA) of 1 kPa between carbon dioxide pressure (PCO(2)) measurements were determined as clinically acceptable. RESULTS: In total 101 'paired' arterial and transcutaneous measurements were obtained from 21 patients. Bias between PaCO(2) and PtcCO(2) was -0.03 kPa with LOA from -0.78 to 0.71 kPa. Bias between SaO(2) and SpO(2) was -1.0% with LOA from -2.83 to 0.83%. CONCLUSIONS: Transcutaneous estimations of PCO(2) and SpO(2) are accurate and can be used in CPET, circumvening the need for arterial cannulation.

Can pulmonary foam arise after postmortem submersion in water? An animal experimental pilot study.

It is difficult to differentiate drowning from postmortem submersion. Pulmonary foam can be found in bodies retrieved from water. It is unknown whether foam is a result of drowning or if it also forms after postmortem submersion. We divided deceased piglets into three groups: postmortem saltwater submersion (N = 20), postmortem freshwater submersion (N = 20) and dry-land controls (N = 20). All carcasses underwent endoscopic examination within 24 h of death and the presence of external and internal pulmonary foam was scored. No external foam was detected in the postmortem freshwater or the postmortem saltwater group. Internal foam was seen in 35% of the postmortem freshwater and 40% of the postmortem saltwater group. No external or internal foam was detected in the dry land control group. The literature shows external as well as internal foam in drowned humans. Internal foam is seen in postmortem submersion in the current piglet study and antemortem submersion in the literature in humans, and can therefore not be used to support/refute the diagnosis of drowning. No external foam was present in the postmortem submersed piglets, yet has been described in drowned humans. Hence the presence of external foam in bodies recovered from water may be indicative for drowning. The presence of external foam is a potentially valuable clinical sign in distinguishing drowning from postmortem submersion.

Sleep, hypnotics and chronic obstructive pulmonary disease.

The quality of sleep is significantly compromised in many patients with chronic obstructive pulmonary disease (COPD) and may be further diminished when certain comorbidities are present. A reduced sleep quality is associated with daytime consequences like fatigue, psychiatric problems and an impaired quality of life. Sleep induces physiologic alterations in respiratory function, which can become pathologic and may provoke or worsen hypoxemia and hypercapnia in COPD. Dyspnea, cough and excessive mucus production should be optimised to minimise causes for sleep disturbance. Pharmacological therapy may be helpful; sedatives like benzodiazepines and non-benzodiazepine benzodiazepine-receptor agonists (NBBRAs) are (equally) effective in improving sleep quality. Whether or not these hypnotics produce serious adverse respiratory effects during sleep, remains unclear due to opposing studies. Therefore, their use should be as short as possible.

An Integral assessment framework of health status in chronic obstructive pulmonary disease (COPD).

BACKGROUND: To date, many health status instruments exist, but the validity of these instruments is questionable. This is caused by the fact that health status is poorly defined. PURPOSE: To develop a validated framework that improves conceptual insight into health status and its domains. METHODS: Based on theoretical and clinical considerations, we defined the domains of health status into concrete sub-domains by formulating conceptual models. Guided by these conceptual models, for each sub-domain, existing instruments were selected. We validated the conceptual models in the data of 168 COPD patients. Using factor analysis, underlying concepts in the data were identified. RESULTS: The resulting framework included physiological functioning, complaints, functional impairment, and quality of life. These main domains were shown to be subdivided into 15 sub-domains. CONCLUSIONS: The present study shows that health status consists of conceptually distinct sub-domains. Integral assessment of health status thus entails measuring all sub-domains. Existing instruments measure only few sub-domains. Integral assessment of health status thus requires the combination of different instruments. The present framework of health status can help in composing such a battery of instruments. Patient profiles obtained by the framework are essential in individualizing treatment.

Exercise performance improves in patients with COPD due to respiratory muscle endurance training.

BACKGROUND: Impaired exercise tolerance is frequently observed in patients with COPD. Respiratory muscle endurance training (RMET) by means of normocapnic hyperpnea can be used to improve respiratory muscle function and probably exercise capacity. RMET is not applied on a large scale because complicated equipment is needed to maintain carbon dioxide homeostasis during hyperpnea, which can also be done by enlarging the dead space of the ventilatory system by breathing through a tube. Therefore, tube breathing might be a new, inexpensive method for home-based RMET. The aim of this study was to assess whether home-based RMET by means of tube breathing improves endurance exercise performance in patients with COPD. METHODS: We randomized 36 patients with moderate-to-severe COPD to RMET by paced tube breathing (n = 18) or sham training (control, n = 18). Both groups trained twice daily for 15 min, 7 days per week, for 5 weeks. RESULTS: Patients receiving RMET showed significant improvements in endurance exercise capacity (constant-load exercise on cycle ergometry; 18 min vs 28 min, p < 0.001), in perception of dyspnea (Borg score; 8.4 vs 5.4, p < 0.001), and respiratory muscle endurance capacity (sustainable inspiratory pressure; 25 cm H(2)O vs 31 cm H(2)O, p = 0.005). Quality of life (chronic respiratory disease questionnaire) also improved (78.7 to 86.6, p = 0.001). The control group showed no significant changes. CONCLUSION: Home-based RMET by means of tube breathing leads to a significant improvement of endurance exercise capacity, a reduction in perception of dyspnea, and an improvement in quality of life in patients with moderate-to-severe COPD.

Tube breathing as a new potential method to perform respiratory muscle training: safety in healthy volunteers.

Normocapnic hyperpnea has been established as a method of respiratory muscle endurance training (RMET). This technique has not been applied on a large scale because complicated and expensive equipment is needed to maintain CO(2)-homeostasis during hyperpnea. This CO(2)-homeostasis can be preserved during hyperpnea by enlarging the dead space of the ventilatory system. One of the possibilities to enlarge dead space is breathing through a tube. If tube breathing is safe and feasible, it may be a new and inexpensive method for RMET, enabling its widespread use. The aim of this study was to evaluate the safety of tube breathing and investigate the effect on CO(2)-homeostasis in healthy subjects. A total of 20 healthy volunteers performed 10 min of tube breathing (dead space 60% of vital capacity). Oxygen-saturation, PaCO(2), respiratory muscle function, hypercapnic ventilatory response and dyspnea (Borg-score) were measured. Tube breathing did not lead to severe complaints, adverse events or oxygen desaturations. A total of 14 out of 20 subjects became hypercapnic (PaCO(2)>6.0 kPa) during tube breathing. There were no significant correlations between PaCO(2) and respiratory muscle function or hypercapnic ventilatory responses. The normocapnic versus hypercapnic subjects showed no significant differences between decrease in oxygen saturation (-0.7% versus -0.2%, respectively, P=0.6), Borg score (4.3 versus 4.7, P=0.9), respiratory muscle function nor hypercapnic ventilatory responses. Our results show that tube breathing is well tolerated amongst healthy subjects. No complaints, nor desaturations occurred. Hypercapnia developed in a substantial number of subjects. When tube breathing will be applied as respiratory muscle training modality, this potential development of hypercapnia must be considered.

Effects of delayed psychosocial interventions versus early psychosocial interventions for women with early stage breast cancer.

OBJECTIVE: The importance of psychosocial counselling after a diagnosis of cancer has been acknowledged and many intervention studies have been carried out, with the aim to find out which types of intervention are most effective in enhancing quality of life in cancer patients. A factor which could be part of effective counselling could be the time of offering psychosocial counselling. The aim of this study was to research the effect of time of enrolment in a psychosocial group intervention on psychosocial adjustment. METHODS: In the present study, 67 women with early stage breast cancer were randomised in a psychosocial group intervention program starting within 4 months after surgery or in the same intervention program starting at least 3 months later. RESULTS: The main conclusion of this study is that women who started with their intervention early were less distressed at 6 months follow-up than women who were in the delayed condition. Medical and demographic variables were predictive for some psychosocial adjustment indicators, but were not associated with time of enrolment. Regardless of time of enrolment, women improved in distress, body image and recreational activities, but showed a decrease in social interaction. CONCLUSION: Though results are limited, based on these results we suggest that psychosocial counselling should be offered as soon after diagnosis or surgery for breast cancer. PRACTICE IMPLICATIONS: Women diagnosed with primary breast cancer should be able to start with psychological counselling soon after being diagnosed, to prevent them from becoming distressed at long term.

Using the Lower Limit of Normal Instead of the Conventional Cutoff Values to Define Predictors of Pulmonary Function Impairment in Subjects With Chronic Heart Failure.

BACKGROUND: Using the newer lower limit of normal criterion instead of the conventional cutoff values to define pulmonary function abnormalities may result in different predictors of pulmonary function impairment in patients with heart failure. Therefore, we assessed predictors of pulmonary function impairment in subjects with chronic heart failure according to the lower limit of normal in comparison with conventional cutoff values. METHODS: In this prospective cross-sectional study, 164 chronic heart failure subjects (age 68 ± 10 y, 78% men, 88% New York Heart Association class I-II) with left ventricular ejection fraction <40% underwent pulmonary function tests. Predictors of pulmonary function impairment were assessed using the lower limit of normal and conventional cutoff values (ie, 80% predicted value and the fixed ratio of FEV1/FVC <0.7). RESULTS: The lower limit of normal criterion identified an extra independent predictor of diffusion impairment compared with the 80% predicted value; in addition to body mass index, pack-years, and alveolar volume, female sex also turned out to be an independent predictor. A smoking history of ≥10 pack-years was a significant predictor of diffusion impairment and airway obstruction using the lower limit of normal criterion but not using the conventional cutoff values. However, lowering the cutoff points of conventional criteria to match the more stringent lower limit of normal and thus avoid overdiagnosis of diffusion impairment and airway obstruction in the elderly produced similar results as the lower limit of normal. CONCLUSIONS: The lower limit of normal identifies more predictors of diffusion impairment and airway obstruction compared with conventional cutoff values in subjects with chronic heart failure with left ventricular systolic dysfunction. However, lowering the conventional cutoff points yielded similar results as the lower limit of normal. (ClinicalTrials.gov registration NCT01429376.).

Comparison of acetazolamide and medroxyprogesterone as respiratory stimulants in hypercapnic patients with COPD.

BACKGROUND: Acetazolamide and medroxyprogesterone acetate (MPA) are two respiratory stimulants that can be used in patients with stable hypercapnic COPD. DESIGN AND METHODS: The effects of acetazolamide, 250 mg bid, and MPA, 30 mg bid, on daytime and nighttime blood gas values and the influences on the hypercapnic and hypoxic ventilatory and mouth occlusion pressure (P(0.1)) at 100 ms response were studied in a crossover design in 12 hypercapnic patients with stable COPD (FEV(1), 33 +/- 4% predicted [mean +/- SEM]). RESULTS: Daytime PaCO(2) decreased from 47.3 +/- 0.8 mm Hg (placebo) to 42.0 +/- 1.5 mm Hg during acetazolamide treatment (p < 0.05) and to 42.8 +/- 1.5 mm Hg during MPA treatment (p < 0.05). Daytime PaO(2) improved with acetazolamide from 65.2 +/- 2.3 to 75.0 +/- 3.0 mm Hg (p < 0.05), whereas no significant changes were seen with MPA. Mean nocturnal end-tidal carbon dioxide tension decreased with both treatments, from 42.0 +/- 2.3 to 35.3 +/- 2.3 mm Hg with acetazolamide (p < 0.05) and to 34.5 +/- 0.8 mm Hg with MPA (p < 0.05). The percentage of time that the nocturnal arterial oxygen saturation was < 90% was reduced significantly with acetazolamide, from 34.9 +/- 10.7% to 16.3 +/- 7.5% (p < 0.05). Mean nocturnal saturation did not change with MPA. Resting minute ventilation increased significantly only with MPA from 9.6 +/- 0.7 to 10.8 +/- 0.8 L/min (p < 0.05). The slope of the hypercapnic ventilatory response did not change during acetazolamide and MPA therapy. The hypoxic ventilatory response increased from - 0.2 +/- 0.05 to - 0.4 +/- 0.1 L/min/% during acetazolamide (p < 0.05) and to - 0.3 +/- 0.1 L/min/% during MPA (p < 0.05). The hypoxic P(0.1) response improved with acetazolamide treatment from - 0.05 +/- 0.008 to - 0.15 +/- 0.02 mm Hg/% (p < 0.05). CONCLUSIONS: This study shows that acetazolamide and MPA both have favorable effects on daytime and nighttime blood gas parameters in ventilatory-limited patients with stable COPD. However, the use of acetazolamide is preferred because of its extra effect on nocturnal saturation.

Serial pulmonary function tests to diagnose COPD in chronic heart failure.

BACKGROUND: It is unknown whether serial pulmonary function tests are necessary for the correct diagnosis of chronic obstructive pulmonary disease (COPD) in patients with stable non-congested chronic heart failure (CHF). The aim of this study was to determine the prevalence of COPD in outpatients with stable CHF without pulmonary congestion using initial as well as confirmatory spirometry three months after treatment for COPD. METHODS: Spirometry was performed in 187 outpatients with stable CHF without pulmonary congestion on chest radiograph who had a left ventricular ejection fraction < 40% (mean age 69 ± 10 years, 78% men). COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. The diagnosis of COPD was confirmed three months after treatment with tiotropium in newly diagnosed COPD patients. RESULTS: Using a three month follow-up spirometry to confirm initial diagnosis of de novo COPD did not change COPD prevalence significantly: 32.6% initially versus 32.1% after three months of follow-up. Only 1 of 25 (4%) patients with newly diagnosed COPD was not reproducibly obstructed at follow-up. COPD was greatly under- (19%) and overdiagnosed (32%). CONCLUSIONS: Spirometry should be used under stable and euvolemic conditions to decrease the burden of undiagnosed or overdiagnosed COPD in patients with CHF. Under these conditions, a confirmatory spirometry is unnecessary, as it does not change a newly established diagnosis of COPD in the vast majority of patients with CHF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01429376.

Pulmonary function impairment in patients with chronic heart failure: lower limit of normal versus conventional cutoff values.

OBJECTIVE: To determine the prevalence of pulmonary function abnormalities in patients with chronic heart failure (HF) according to recent American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines using the lower limit of normal (LLN) compared to conventional cutoff values. BACKGROUND: Recent ATS/ERS guidelines recommend the use of the LLN instead of the conventional cutoff values to define pulmonary function impairment to avoid misclassification of patients. However, studies addressing the prevalence of pulmonary function abnormalities according to both definitions in patients with chronic HF are lacking. METHODS: In this prospective cross-sectional study, 164 chronic HF outpatients (age 68 ± 10 years, 78% men, 88% New York Heart Association class I-II) with left ventricular ejection fraction < 40% underwent spirometry and measurement of diffusing capacity. Body plethysmography was performed in patients with abnormal spirometry results. RESULTS: Diffusion impairment and airway obstruction were found in 44-58% and 26-37% of the patients, respectively, depending on the definition used (LLN versus conventional cutoff values, p < 0.05). However, restriction was infrequent, irrespective of the definition used (7% versus 5%, respectively, p > 0.05). The LLN identified fewer patients with abnormal lung function, whereas the conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category. Twenty-seven percent of patients were misclassified by the conventional cutoff values. CONCLUSION: Pulmonary function abnormalities, especially diffusion impairment and airway obstruction, were highly prevalent in patients with chronic HF. Conventional cutoff values classified more patients with diffusion impairment, airway obstruction, or a mixed category compared to the LLN.

Bronchodilator responsiveness in patients with chronic heart failure.

OBJECTIVE: The aim of this study was to evaluate the effect of inhaled bronchodilators on pulmonary function and dyspnea in patients with chronic heart failure (HF). BACKGROUND: Conflicting data exist on whether bronchodilators may improve pulmonary function and dyspnea in patients with chronic HF. METHODS: In this retrospective observational study we analyzed data of 116 chronic HF outpatients with systolic dysfunction who underwent spirometry and Borg dyspnea measurements before and after inhalation of 400 µg salbutamol and 80 µg ipratropium. Patients with chronic obstructive pulmonary disease (COPD) or asthma were excluded. RESULTS: Bronchodilators fully reversed airway obstruction (AO) in 25 of 64 (39.1%) patients with pre-bronchodilator AO. All spirometric measurements, except for forced vital and inspiratory capacities, improved significantly post-bronchodilation. Absolute and percent improvements in forced expiratory volume in 1 s (FEV1) were more pronounced in patients with persistent AO post-bronchodilation compared to those without AO (0.19 ± 0.18 L and 8.4 ± 7.3% versus 0.11 ± 0.12 L and 4.3 ± 4.0%, p < 0.05). Significant bronchodilator responsiveness of FEV1 (>200 mL and >12%) was noted in 12.1% and was more frequent in patients with persistent AO and fully reversible AO than in those without AO (23.1% and 16.0% versus 1.9%, p < 0.05). We measured a small, albeit significant improvement in dyspnea (0.7 ± 1.2 versus 0.9 ± 1.3, p = 0.002). CONCLUSIONS: Inhaled bronchodilators may have an additional role in the management of patients with chronic HF because of their potential to improve pulmonary function, especially in those with AO. The clinical usefulness and possible adverse events of bronchodilators need to be further established.