Engaging stakeholders to level up COPD care in LMICs: lessons learned from the "Breathe Well" programme in Brazil, China, Georgia, and North Macedonia.

BACKGROUND: Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned. MAIN BODY: Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice. CONCLUSION: Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.

Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments.

BACKGROUND: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation. OBJECTIVE: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries. METHODS: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID. RESULTS: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score. CONCLUSIONS: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables.

Prevalence and factors associated with asthma among adolescents and adults in Uganda: a general population based survey.

BACKGROUND: Recent large-scale population data on the prevalence of asthma and its risk factors are lacking in Uganda. This survey was conducted to address this data gap. METHODS: A general population based survey was conducted among people ≥12 years. A questionnaire was used to collect participants socio-demographics, respiratory symptoms, medical history, and known asthma risk factors. Participants who reported wheeze in the past 12 months, a physician diagnosis of asthma or current use of asthma medications were classified as having asthma. Asthmatics who were ≥ 35 years underwent spirometry to determine how many had fixed airflow obstruction (i.e. post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio < lower limit of normal (LLN). Descriptive statistics were used to summarize participants' characteristics. Prevalence of asthma was calculated as a proportion of asthmatics over total survey population. To obtain factors independently associated with asthma, a random-effects model was fitted to the data. RESULTS: Of the 3416 participants surveyed, 61.2% (2088) were female, median age was 30 years (IQR, 20-45) and 323 were found to have asthma. Sixteen people with asthma ≥35 years had fixed airflow obstruction. The prevalence of asthma was 11.0% (95% CI:8.9-13.2; males 10.3%, females 11.4%, urban 13.0% and rural 8.9%. Significantly more people with asthma smoked than non-asthmatics: 14.2% vs. 6.3%, p < 0.001, were exposed to biomass smoke: 28.0% vs. 20.0%, p < 0.001, had family history of asthma: 26.9% vs. 9.4%, p, < 0.001, had history of TB: 3.1% vs. 1.30%, p = 0.01, and had hypertension: 17.9% vs. 12.0%, p = 0. 003. In multivariate analysis smoking, (adjusted odds ratio (AOR), 3.26 (1.96-5.41, p < 0.001) family history of asthma, AOR 2.90 (98-4.22 p- < 0.001), nasal congestion, AOR 3.56 (2.51-5.06, p < 0.001), biomass smoke exposure, AOR 2.04 (1.29-3.21, p = 0.002) and urban residence, AOR 2.01(1.23-3.27, p = 0.005) were independently associated with asthma. CONCLUSION: Asthma is common in Uganda and is associated with smoking, biomass smoke exposure, urbanization, and allergic diseases. Health care systems should be strengthened to provide asthma care. Measures to reduce exposure to the identified associated factors are needed.

Rates of asthma exacerbations and mortality and associated factors in Uganda: a 2-year prospective cohort study.

Data on asthma treatment outcomes in Africa are limited. 449 patients with asthma (age 5-93 years) in Uganda were followed up for 2 years to determine rates of exacerbations and mortality and associated factors. During follow-up the median number of exacerbations per patient was 1 (IQR 0-5) and 17 patients died (3.7%, 27.3 deaths per 1000 person years). Considering only the first year of follow-up, 59.6% of the patients experienced at least one exacerbation, 32.4% experienced three or more exacerbations. A multivariable model showed that the likelihood of experiencing at least one exacerbation in the first year of follow-up was lower with better baseline asthma control (higher asthma control test (ACT) score), with OR 0.87 (95% CI: 0.82 to 0.93, P=0.000), and was higher with more exacerbations in the year prior to enrolment (OR for log number of exacerbations 1.28, 95% CI: 1.04 to 1.57, P=0.018). Better asthma control (OR 0.93, 95% CI: 0.88 to 0.99, P=0.021) and number of baseline exacerbations (OR 1.35,95% CI: 1.11 to 1.66, P=0.005) were also the only factors that were independently associated with experiencing three or more exacerbations during the first year of follow-up. The only factor found to be associated with all-cause mortality was FEV1, with higher recent FEV1 associated with lower all-cause mortality (OR 0.30, 95% CI: 0.14 to 0.65; P=0.002). Rates of asthma exacerbations and mortality are high in Uganda and are associated with poor asthma control. Health systems should be strengthened to care for asthma patients.

Clinically relevant differences in COPD health status: systematic review and triangulation.

The minimal clinically important difference (MCID) quantifies when measured differences can be considered clinically relevant. This study aims to review and triangulate MCIDs of chronic obstructive pulmonary disease (COPD) health status tools.A systematic search in PubMed, EMBASE and Cochrane Library was conducted (Prospero #CRD42015023221). Study details, patient characteristics, MCID methodology and estimates were assessed and extracted by two authors. A triangulated mean was obtained for each tool's MCID, with two-thirds weighting for anchor-based and one-third for distribution-based results. This was then multiplied by a weighted factor based upon the study size and quality rating.Overall, 785 records were reviewed of which 21 studies were included for analysis. MCIDs of 12 tools were presented. General quality and risk of bias were average to good. Triangulated MCIDs for the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ) were -2.54, -0.43 and -7.43 for improvement. Too few and/or too diverse studies were present to triangulate MCIDs of other tools.Evidence for the MCID of the CAT and CCQ was strong and triangulation was valid. Currently used MCIDs in clinical practice for the SGRQ (4) and Chronic Respiratory Questionnaire (0.5) did not match the reviewed content, for which the MCIDs were much higher. Using too low MCIDs may lead to an overestimation of the interpretation of treatment effects. MCIDs for deterioration were scarce, which highlights the need for more research.

Inspiratory muscle training does not improve clinical outcomes in 3-week COPD rehabilitation: results from a randomised controlled trial.

The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled trial examined the effectiveness of IMT added to pulmonary rehabilitation.In total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received a 3-week inpatient pulmonary rehabilitation, of which 602 patients were included in the intention-to-treat analyses. The intervention group (n=300) received highly intensive IMT and the control group (n=302) received sham IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary outcomes were 6-min walk distance, dyspnoea, quality of life and lung function. Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was used.The intervention group showed higher effects in PImax (p<0.001) and forced inspiratory volume in 1 s (p=0.013). All other outcomes in both study groups improved significantly, but without further between-group differences. Sex and pulmonary rehabilitation admission shortly after hospitalisation modified quality of life effects.IMT as an add-on to a 3-week pulmonary rehabilitation improves inspiratory muscle strength, but does not provide additional benefits in terms of exercise capacity, quality of life or dyspnoea. A general recommendation for COPD patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.

The impact of HIV on the prevalence of asthma in Uganda: a general population survey.

BACKGROUND: HIV and asthma are highly prevalent diseases in Africa but few studies have assessed the impact of HIV on asthma prevalence in high HIV burden settings. The objective of this analysis was to compare the prevalence of asthma among persons living with HIV (PLHIV) and those without HIV participating in the Uganda National Asthma Survey (UNAS). METHODS: UNAS was a population-based survey of persons aged ≥12 years. Asthma was diagnosed based on either self-reported current wheeze concurrently or within the prior 12 months; physician diagnosis; or use of asthma medication. HIV was defined based on confidential self-report. We used Poisson regression with robust standard errors to estimate asthma prevalence and the prevalence ratio (PR) for HIV and asthma. RESULTS: Of 3416 participants, 2067 (60.5%) knew their HIV status and 103 (5.0%) were PLHIV. Asthma prevalence was 15.5% among PLHIV and 9.1% among those without HIV, PR 1.72, (95%CI 1.07-2.75, p = 0.025). HIV modified the association of asthma with the following factors, PLHIV vs. not PLHIV: tobacco smoking (12% vs. 8%, p = < 0.001), biomass use (11% vs. 7%, p = < 0.001), allergy (17% vs. 11%, p = < 0.001), family history of asthma (17% vs. 11%, p = < 0.001), and prior TB treatment (15% vs. 10%, p = < 0.001). CONCLUSION: In Uganda the prevalence of asthma is higher in PLHIV than in those without HIV, and HIV interacts synergistically with other known asthma risk factors. Additional studies should explore the mechanisms underlying these associations. Clinicians should consider asthma as a possible diagnosis in PLHIV presenting with respiratory symptoms.

The PROactive instruments to measure physical activity in patients with chronic obstructive pulmonary disease.

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients.

The PROactive innovative conceptual framework on physical activity.

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what "physical activity" means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients' perspective. The PROactive PRO instruments' content validity represents the pivotal basis for empirically based item reduction and validation.

The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Real-world walking cadence in people with COPD.

Introduction: The clinical validity of real-world walking cadence in people with COPD is unsettled. Our objective was to assess the levels, variability and association with clinically relevant COPD characteristics and outcomes of real-world walking cadence. Methods: We assessed walking cadence (steps per minute during walking bouts longer than 10 s) from 7 days' accelerometer data in 593 individuals with COPD from five European countries, and clinical and functional characteristics from validated questionnaires and standardised tests. Severe exacerbations during a 12-month follow-up were recorded from patient reports and medical registries. Results: Participants were mostly male (80%) and had mean±sd age of 68±8 years, post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57±19% predicted and walked 6880±3926 steps·day-1. Mean walking cadence was 88±9 steps·min-1, followed a normal distribution and was highly stable within-person (intraclass correlation coefficient 0.92, 95% CI 0.90-0.93). After adjusting for age, sex, height and number of walking bouts in fractional polynomial or linear regressions, walking cadence was positively associated with FEV1, 6-min walk distance, physical activity (steps·day-1, time in moderate-to-vigorous physical activity, vector magnitude units, walking time, intensity during locomotion), physical activity experience and health-related quality of life and negatively associated with breathlessness and depression (all p<0.05). These associations remained after further adjustment for daily steps. In negative binomial regression adjusted for multiple confounders, walking cadence related to lower number of severe exacerbations during follow-up (incidence rate ratio 0.94 per step·min-1, 95% CI 0.91-0.99, p=0.009). Conclusions: Higher real-world walking cadence is associated with better COPD status and lower severe exacerbations risk, which makes it attractive as a future prognostic marker and clinical outcome.

Minor neurological dysfunction and behaviour in 9-year-old children born at term: evidence for sex dimorphism.

AIM: The aim of the study was to assess associations between minor neurological dysfunction (MND) and behaviour, with specific attention to sex differences. METHOD: This was an observational cohort study in which 341 9-year-old children (177 male, 164 female) without perinatal risk were neurologically assessed, with attention to severity and type of MND. Eight domains of dysfunction were distinguished, including posture and muscle tone, fine manipulative ability and coordination. Severity of MND was based on the number of dysfunctional domains. Behaviour was assessed by parents and teachers using the Child Behavior Checklist and Teacher's Report Form (TRF); outcomes were internalizing and externalizing behaviour and total score of behavioural problems. RESULTS: Females with complex MND or dysfunctional posture and muscle tone had increased risk for externalizing behavioural problems (OR 4.52, 95% CI 1.01-20.2, and OR 4.05, 95% CI 1.06-15.5, respectively). In males, these associations were absent. However, males with simple MND had an increased risk for behavioural problems indicated by the total TRF-score (OR 7.52, 95% CI 1.36-41.4). INTERPRETATION: In children without perinatal risk, associations between MND and behaviour are sex-specific. In females, dysfunction of complex neural networks, including the cerebellum, is associated with externalizing behaviour. In males, neurobehavioural relationships are limited, suggesting a larger role of psychosocial factors in the genesis of behavioural problems.

Putting health status guided COPD management to the test: protocol of the MARCH study.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible and usually progressive. Current guidelines, among which the Dutch, have so far based their management strategy mainly on lung function impairment as measured by FEV1, while it is well known that FEV1 has a poor correlation with almost all features of COPD that matter to patients. Based on this discrepancy the GOLD 2011 update included symptoms and impact in their treatment algorithm proposal. Health status measures capture both symptoms and impact and could therefore be used as a standardized way to capture the information a doctor could otherwise only collect by careful history taking and recording. We hypothesize that a treatment algorithm that is based on a simple validated 10 item health status questionnaire, the Clinical COPD Questionnaire (CCQ), improves health status (as measured by SGRQ) and classical COPD outcomes like exacerbation frequency, patient satisfaction and health care utilization compared to usual care based on guidelines. METHODS/DESIGN: This hypothesis will be tested in a randomized controlled trial (RCT) following 330 patients for two years. During this period general practitioners will receive treatment advices every four months that are based on the patient's health status (in half of the patients, intervention group) or on lung function (the remaining half of the patients, usual care group). DISCUSSION: During the design process, the selection of outcomes and the development of the treatment algorithm were challenging. This is discussed in detail in the manuscript to facilitate researchers in designing future studies in this changing field of implementation research. TRIAL REGISTRATION: Netherlands Trial Register, NTR2643.

Impact of chronic respiratory symptoms in a rural area of sub-Saharan Africa: an in-depth qualitative study in the Masindi district of Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), once regarded as a disease of developed countries, is now recognised as a common disease in low- and middle-income countries. No studies have been performed to examine how the community in resource poor settings of a rural area in sub-Saharan Africa lives with chronic respiratory symptoms. AIMS: To explore beliefs and attitudes concerning health (particularly respiratory illnesses), use of biomass fuels, tobacco smoking, and the use of health services. METHODS: A qualitative study was undertaken in a rural area of Masindi district in Uganda, using focus group discussions with 10-15 members of the community in 10 randomly selected villages. RESULTS: Respiratory symptoms were common among men, women, and children. In several communities respiratory symptoms were stigmatised and often associated with tuberculosis. Almost all the households used firewood for cooking and the majority cooked indoors without any ventilation. The extent of exposure to tobacco and biomass fuel smoke was largely determined by their cultural tradition and gender, tribal origin and socioeconomic factors. Many people were unaware of the damage to respiratory health caused by these risk factors, notably the disproportionate effect of biomass smoke in women and children. CONCLUSIONS: The knowledge of chronic respiratory diseases, particularly COPD, is poor in the rural community in sub-Saharan Africa. The lack of knowledge has created different beliefs and attitudes concerning respiratory symptoms. Few people are aware of the relation between smoke and respiratory health, leading to extensive exposure to mostly biomass-related smoke.

Effects of long-chain polyunsaturated fatty acid supplementation of infant formula on cognition and behaviour at 9 years of age.

AIM: Long-chain polyunsaturated fatty acid (LCPUFA) supplementation of infant formula may have a beneficial effect on cognitive development. This study aimed to investigate the effect of LCPUFA formula supplementation primarily on cognition and secondarily on behaviour at age 9 years. Special attention was paid to the potentially modifying effect of maternal smoking during pregnancy. METHOD: A double-blind, randomized control study was performed in two groups of healthy infants born at term: one group, constituting the control group, received standard formula (n=169) and another group received standard formula supplemented with LCPUFAs (n=146). A breastfed group (n=159) served as an additional reference. At 9 years of age, 72% of the children (control group: n=123; 71 males, 52 females; LCPUFA group: n=91; 42 males, 49 females; breastfed group: n=127, 64 males, 63 females) underwent extensive cognitive and behavioural testing. RESULTS: An interaction between infant nutrition and smoking during pregnancy was found. Among children exposed to smoking during pregnancy, LCPUFA supplementation was associated with higher mean verbal IQ scores (p=0.007) and learning and memory (p=0.006). Among children not exposed to smoking during pregnancy, LCPUFA supplementation was associated with lower mean verbal memory scores (p=0.003). Executive function scores were significantly lower in the LCPUFA-supplemented group than in the control group (p=0.001). Breastfeeding was associated with better performance on IQ (p=0.005). INTERPRETATION: No consistent beneficial effect of LCPUFA formula supplementation on cognitive development in term-born infants was found. The study confirmed that breastfeeding is associated with better cognition.

Improved health status of severe COPD patients after being included in an integrated primary care service: A prospective cohort study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease. It is assumed that severe patients will receive better treatment in specialised care centres but the prevalence of severe COPD in primary care is high. Integrated primary care services combine input from several sources and advice from pulmonologists to provide general practitioners with support needed to improve diagnosis and treatment of patients with COPD. OBJECTIVES: To evaluate patient-reported outcomes and costs of managing patients classified as GOLD D in an integrated primary care service over 12 months. METHODS: Patients were included in this 1-year prospective cohort study if they met the 2014 GOLD D criteria, were aged ≥ 40 years and gave written informed consent for this study. Recruitment took place through the patients' general practitioners. The primary outcome was health status, assessed with the Clinical COPD Questionnaire (CCQ) and COPD Assessment Test (CAT). Secondary outcomes included self-reported exacerbations, quality-adjusted life years and health(care)-related costs. RESULTS: Forty-nine patients were included. At baseline, the mean CAT score was 15.9 and the median CCQ score was 1.7. After 12 months, scores had improved by 2.3 (95% confidence interval, 0.8-3.7) and 0.4 (95% confidence interval, 0.2-0.7), respectively. Percentage of patients with ≥2 exacerbations in the past 12 months also decreased from baseline (77.6%) to 12 months (16.7%). Changes in mean quarterly costs were small. CONCLUSION: An integrated service for COPD based in primary care may improve the health status of patients with a large burden of disease while not increasing health care costs.

The Groningen LCPUFA study: No effect of short-term postnatal long-chain polyunsaturated fatty acids in healthy term infants on cardiovascular and anthropometric development at 9 years.

Conflicting evidence exists on the effect of long-chain polyunsaturated fatty acid (LCPUFA) formula supplementation on cardiovascular health in term infants. It is known that LCPUFA supplementation does not affect infant growth, but long term outcome data are not available. The current study investigates whether 2 mo LCPUFA formula supplementation affects cardiovascular and anthropometric development at 9 y. A prospective, double-blind, randomized trial was performed in healthy term infants: a standard formula control group (CF, n = 169) and a LCPUFA-supplemented group [LF, n = 145; 0.45% (by wt) AA and 0.30% (by wt) docosahexaenoic acid (DHA)]. A breastfed group (BF; n = 159) served as reference. At the age of 9 y, systolic and diastolic blood pressure, heart rate, head circumference, weight, and height were measured. Univariate and multivariate analyses were performed; 63 to 79% of children were assessed. None of the cardiovascular or anthropometric measurements differed between the formula groups. Breastfed children had a marginally lower heart rate than formula-fed children, in particular compared with children fed control formula. Blood pressure and parameters of growth including BMI of breast and formula-fed children did not differ. In conclusion, the study suggests that short-term LCPUFA supplementation does not influence cardiovascular and anthropometric development at 9 y.