Clinical characteristics governing treatment adjustment in COPD patients: results from the Swiss COPD cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a widespread chronic disease characterised by irreversible airway obstruction [1]. Features of clinical practice and healthcare systems for COPD patients can vary widely, even within similar healthcare structures. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy is considered the most reliable guidance for the management of COPD and aims to provide treating physicians with appropriate insight into the disease. COPD treatment adaptation typically mirrors the suggestions within the GOLD guidelines, depending on how the patient has been categorised. However, the present study posits that the reasons for adjusting COPD-related treatment are hugely varied. OBJECTIVES: The objective of this study was to assess the clinical symptoms that govern both pharmacological and non-pharmacological treatment changes in COPD patients. Using this insight, the study offers suggestions for optimising COPD management through the implementation of GOLD guidelines. METHODS: In this observational cohort study, 24 general practitioners screened 260 COPD patients for eligibility from 2015-2019. General practitioners were asked to collect general information from patients using a standardised questionnaire to document symptoms. During a follow-up visit, the patient's symptoms and changes in therapy were assessed and entered into a central electronic database. Sixty-five patients were removed from the analysis due to exclusion criteria, and 195 patients with at least one additional visit within one year of the baseline visit were included in the analysis. A change in therapy was defined as a change in either medication or non-medical treatment, such as pulmonary rehabilitation. Multivariable mixed models were used to identify associations between given symptoms and a step up in therapy, a step down, or a step up and a step down at the same time. RESULTS: For the 195 patients included in analyses, a treatment adjustment was made during 28% of visits. In 49% of these adjustments, the change in therapy was a step up, in 33% a step down and in 18% a step up (an increase) of certain treatment factors and a step down (a reduction) of other prescribed treatments at the same time. In the multivariable analysis, we found that the severity of disease was linked to the probability of therapy adjustment: patients in GOLD Group C were more likely to experience an increase in therapy compared to patients in GOLD Group A (odds ratio [OR] 3.43 [95% confidence interval {CI}: 1.02-11.55; p = 0.135]). In addition, compared to patients with mild obstruction, patients with severe (OR 4.24 [95% CI: 1.88-9.56]) to very severe (OR 5.48 [95% CI: 1.31-22.96]) obstruction were more likely to experience a therapy increase (p <0.0001). Patients with comorbidities were less likely to experience a treatment increase than those without (OR 0.42 [95% CI: 0.24-0.73; p = 0.002]). A therapy decrease was associated with both a unit increase in COPD Assessment Test (CAT) score (OR 1.07 [95% CI: 1.01-1.14; p = 0.014]) and having experienced an exacerbation (OR 2.66 [95% CI: 1.01-6.97; p = 0.047]). The combination of steps up as well as steps down in therapy was predicted by exacerbation (OR 8.93 [95% CI: 1.16-68.28; p = 0.035]) and very severe obstruction (OR 589 [95% CI: 2.72 - >999; p = 0.109]). CONCLUSIONS: This cohort study provides insight into the management of patients with COPD in a primary care setting. COPD Group C and airflow limitation GOLD 3-4 were both associated with an increase in COPD treatment. In patients with comorbidities, there were often no treatment changes. Exacerbations did not make therapy increases more probable. The presence of neither cough/sputum nor high CAT scores was associated with a step up in treatment.

Risk Factors for Recurrent Exacerbations in the General-Practitioner-Based Swiss Chronic Obstructive Pulmonary Disease (COPD) Cohort.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP-based Swiss COPD cohort and develop a statistical model for predicting exacerbation. METHODS: COPD cohort demographic and medical data were recorded for 24 months, by means of a questionnaire-based COPD cohort. The data were split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and its overall performance was validated. A nomogram was created to facilitate the clinical use of the model. RESULTS: Of the 229 COPD patients analyzed, 77% of the patients did not experience exacerbation during the follow-up. The best subset in the training dataset revealed that lower forced expiratory volume, high scores on the MRC dyspnea scale, exacerbation history, and being on a combination therapy of LABA + ICS (long-acting beta-agonists + Inhaled Corticosteroids) or LAMA + LABA (Long-acting muscarinic receptor antagonists + long-acting beta-agonists) at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) value was 0.75 for one or more exacerbations. The calibration was accurate (0.34 predicted exacerbations vs 0.28 observed exacerbations). CONCLUSION: Nomograms built from these models can assist clinicians in the decision-making process of COPD care.

Comparative analysis of NK cell subsets in menstrual and peripheral blood of patients with unexplained recurrent spontaneous abortion and fertile subjects.

Natural killer (NK) cells play a fundamental role in maintaining pregnancy. Based on the availability and non-invasive method of collection of menstrual blood (MB), here we investigated for the first time a comparative analysis of NK cell subsets in MB and peripheral blood (PB) of women with recurrent spontaneous abortion (RSA) and fertile women. PB and MB of healthy fertile (n=15) and RSA women (n=15) were sampled simultaneously on the second day of the menstrual cycle. Proportions of CD56+CD3-CD16+/-, CD56+CD3-CCR7+/-, and CD56+CD3-CD45RO+/- cells were analyzed using flow cytometry. In the MB of both groups, proportions of CD16+ and CD45RO- NK cells were significantly lower than in the PB. In parallel, CD56+CD16+CCR7- and CCR7+ cells were present in significantly smaller amounts in MB than in PB. However, the amounts of CD56+CD16-CCR7- and CCR7+ cells were greater in MB. In comparison to the fertile group, the percentage of MB CD45RO+ NK cells was significantly lower and frequencies of PB CD16-, CD45RO- and CD56+CD16+CCR7+ subsets were significantly higher in RSA patients. Different subsets of NK cells are differentially distributed in MB in comparison with PB in women with RSA and fertile subjects. Population differences of NK cell subsets in RSA patients and normal controls were more clearly reflected at the systemic level.

Association between plasminogen activator inhibitor 1 gene mutation and different subgroups of recurrent miscarriage and implantation failure.

PURPOSE: To compare plasminogen activator inhibitor type1 (PAI-1) mutation rates in different groups of patients with the record of recurrent miscarriage (RM) or implantation failure (IF) with special emphasis on the number of missed pregnancies and/or implantation failures (RM ≥ 2, IF ≥ 2, RM + IF ≥ 2, RM ≥ 3, IF ≥ 3 and RM + IF ≥ 3). METHOD: Case-control study from PCR products and RFLP data of DNA from blood of patients who referred to the infertility clinic including 595 patients (421 RM ≥ 2, 119 IF ≥ 2 and 55 RM + IF ≥ 2) as the case groups and 100 healthy women as the control group. RESULTS: All six different subgroups of patients showed increased frequencies of the mutant allele (4G) in comparison to the control group (p < 0.001) suggesting a role for PAI-1 mutation in RM and IF. CONCLUSIONS: The different patient subgroups suffer similar rates of risk in developing RM and IF when compared to controls.