Chronic airflow obstruction attributable to poverty in the multinational Burden of Obstructive Lung Disease (BOLD) study.

Poverty is strongly associated with all-cause and chronic obstructive pulmonary disease (COPD) mortality. Less is known about the contribution of poverty to spirometrically defined chronic airflow obstruction (CAO)-a key characteristic of COPD. Using cross-sectional data from an asset-based questionnaire to define poverty in 21 sites of the Burden of Obstructive Lung Disease study, we estimated the risk of CAO attributable to poverty. Up to 6% of the population over 40 years had CAO attributable to poverty. Understanding the relationship between poverty and CAO might suggest ways to improve lung health, especially in low-income and middle-income countries.

Chronic airflow obstruction and ambient particulate air pollution.

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.

Does the 'slipping slipper sign' in patients with diabetes predict the presence of retinopathy and nephropathy?

BACKGROUND: Previous research had noted that an affirmative response in patients with diabetes to the question 'Have you ever lost your slipper/flip-flop from your feet while walking and not realised that you have done so'? That is, the presence of the 'slipping slipper sign' (SSS) reflected the presence of severe diabetic peripheral neuropathy with a high degree of precision. The objective of the current study was to determine whether the SSS may also predict the presence of diabetic retinopathy and/or nephropathy since microvascular complications are known to cosegregate. SUBJECTS AND METHODS: Among 100 patients with diabetes, including 33 cases with the SSS and 67 controls without the SSS, data on demography, dipstick proteinuria as well as the presence and staging of diabetic retinopathy were obtained. RESULTS: The mean (SD) age of all patients was 54.6 (13.0) years, mean duration of diabetes was 12.7 (10.2) years and mean haemoglobin A1c (HbA1c) 8.42 (1.95) %; 43% were males. All 33 (100%) of the patients with SSS but only 12 (18%) of the patients without SSS were found to exhibit diabetic retinopathy, p<0.001. Among those patients with retinopathy, proliferative retinopathy was far more likely (39%) in the SSS group compared with non-SSS subjects (8%). Similarly, 15 (46%) with SSS and only 4 (6%) without SSS were found to have dipstick proteinuria. The sensitivity of the SSS for retinopathy was 73% and the specificity was 100% with a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 82%. For proteinuria, both the sensitivity and specificity was 78%. CONCLUSIONS: Both diabetic retinopathy and dipstick proteinuria are strongly associated with the presence of the SSS that therefore holds potential as a tool for easier identification of this high-risk group.

Reality and understanding of asthma control.

The aim of this study was to describe the level and perception of control in severe asthma in Trinidad after the introduction of revised guidelines for asthma management. Adult asthmatics (N = 329) at Trinidad's chest clinics were cross-sectionally examined for guideline-defined disease control. Patients' mean (SD) age was 54.36 (14.9) years, with body mass index = 28.54 (7.4) kg/meter(2), and females were proportionally more (246, 74.74%). Measured (45.29%) and perceived (18.96%) uncontrolled disease were poorly concordant (κ statistic = 0.197). Co-morbidity (≥2 conditions) correlated with uncontrolled disease in 55.80% of patients (Spearman correlation p = 0.03). Absolute peak expiratory flow was higher (p < 0.001) in controlled and/or partially controlled disease than in uncontrolled asthma. Routine work limitation, night-time disturbances, work absenteeism, exacerbations, rescue inhalation and perceived control correlated with uncontrolled asthma (p < 0.001). Few patients self-monitored lung function (9.73%) or kept an asthma diary (6.69%), but 65.1% believed they had to live with their symptoms. The asthma burden was at least one hospitalization (53.80%) and emergency department visit (66.36%) in the past year, cough (74.49%), dyspnoea (84.50%), wheezing (80.55%) and chest tightness (66.87%). After the revised guidelines, uncontrolled asthma and related morbidity remain suboptimal, with disagreeing actual and perceived control. Efforts to transform guidelines into patient care with realistic interpretation of control are recommended.

FOMO (fate of online media only) in infectious disease modeling: a review of compartmental models.

Mathematical models played in a major role in guiding policy decisions during the COVID-19 pandemic. These models while focusing on the spread and containment of the disease, largely ignored the impact of media on the disease transmission. Media plays a major role in shaping opinions, attitudes and perspectives and as the number of people online increases, online media are fast becoming a major source for news and health related information and advice. Consequently, they may influence behavior and in due course disease dynamics. Unlike traditional media, online media are themselves driven and influenced by their users and thus have unique features. The main techniques used to incorporate online media mathematically into compartmental models, with particular reference to the ongoing COVID-19 pandemic are reviewed. In doing so, features specific to online media that have yet to be fully integrated into compartmental models such as misinformation, different time scales with regards to disease transmission and information, time delays, information super spreaders, the predatory nature of online media and other factors are identified together with recommendations for their incorporation.

The role of bronchodilator treatment in the prevention of exacerbations of COPD.

Exacerbations of chronic obstructive pulmonary disease (COPD) are natural events in the progression of the disease, and are characterised by acute worsening of symptoms, especially dyspnoea. These heterogeneous events follow increased airway inflammation, often due to infection, and lead to decreased airflow and increased lung hyperinflation relative to stable COPD. Although exacerbation frequency generally increases as COPD progresses, some patients experience frequent exacerbations (≥ 2 per year) independently of disease severity. Exacerbations, especially frequent exacerbations, are associated with impaired health-related quality of life, reduced physical activity and poor disease prognosis. The cornerstone of pharmacotherapy for stable COPD is long-acting bronchodilators, including the long-acting ß(2)-agonists (LABAs) and long-acting anti-muscarinic agents (LAMAs) alone or combined with inhaled corticosteroids (ICS). While ICS treatment can potentially reduce the risk of exacerbations, clinical studies have demonstrated the efficacy of LABAs and LAMAs in reducing COPD symptoms, primarily by reducing lung hyperinflation secondary to reduced airway resistance. Sustained reduction in lung hyperinflation may in turn lessen dyspnoea during an exacerbation. Indeed, recent studies suggest that bronchodilators may also reduce the incidence of, or prevent, exacerbations. Using data from recent studies, this review explores the evidence and possible mechanisms through which bronchodilators may prevent exacerbations.

Detrended fluctuation analysis of peak expiratory flow and exacerbation frequency in COPD.

We investigated whether exacerbation frequency in chronic obstructive pulmonary disease (COPD) was related to an exponent α which quantifies self-similarity in daily peak expiratory flow (PEF) and is calculated using detrended fluctuation analysis (DFA). We examined data from COPD patients who recorded an increase in respiratory symptoms and post-bronchodilator PEF on daily diary cards. We also investigated PEF data from a double-blind, placebo-controlled trial of the anti-cholinergic agent, tiotropium. In the observational study there were 308 patients with COPD (195 males; mean ± sd age 68.3 ± 8.4 yrs, forced expiratory volume in 1 s (FEV(1)) 1.12 ± 0.46 L, FEV(1) % predicted 44.5 ± 16.4%). The mean ± sd α over the first year was 0.944 ± 0.19 and it was positively related to the frequency of exacerbations per year (p=0.009). In the clinical trial, α was lower in COPD patients randomised to tiotropium, mean ± sd 0.87 ± 0.21 (n=48) than on placebo, mean ± sd 0.95 ± 0.19 (n=52; p=0.035). Power analysis showed that fewer patients would be required for clinical studies with α as the outcome measure than exacerbation frequency. DFA shows that daily PEF in COPD has long-term correlations which are related to exacerbation frequency. Monitoring of PEF and use of α may result in smaller COPD patient sample sizes in trials.

Outdoor air pollution and respiratory health in patients with COPD.

OBJECTIVES: Time series studies have shown adverse effects of outdoor air pollution on mortality and hospital admissions in patients with chronic obstructive pulmonary disease (COPD) but panel studies have been inconsistent. This study investigates short-term effects of outdoor nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM(10)) and black smoke on exacerbations, respiratory symptoms and lung function in 94 patients with COPD in east London. METHODS: Patients were recruited from an outpatient clinic and were asked to complete daily diary cards (median follow-up 518 days) recording exacerbations, symptoms and lung function, and the amount of time spent outdoors. Outdoor air pollution exposure (lag 1 day) was obtained from local background monitoring stations. RESULTS: Symptoms but not lung function showed associations with raised pollution levels. Dyspnoea was significantly associated with PM(10) (increase in odds for an IQR change in pollutant: 13% (95% CI 4% to 23%)) and this association remained after adjustment for other the pollutants measured. An IQR increase in nitrogen dioxide was associated with a 6% (0-13%) increase in the odds of a symptomatic fall in peak flow rate. The corresponding effect sizes for PM(10) and black smoke were 12% (2-25%) and 7% (1-13%), respectively. CONCLUSION: It is concluded that outdoor air pollution is associated with important adverse effects on symptoms in patients with COPD living in London.

The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide.

RATIONALE: Exacerbations are key drivers of morbidity and mortality in chronic obstructive pulmonary disease (COPD). OBJECTIVES: We compared the relative efficacy of the long-acting inhaled bronchodilator/antiinflammatory combination (salmeterol/fluticasone propionate) 50/500 microg twice daily and the long-acting bronchodilator (tiotropium) 18 microg once daily in preventing exacerbations and related outcomes in severe and very severe COPD. METHODS: A total of 1,323 patients (mean age, 64 yr, post-bronchodilator FEV1, 39% predicted) were randomized in this 2-year, double-blind, double-dummy parallel study. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was health care utilization exacerbation rate. Other endpoints included health status measured by St. George's Respiratory Questionnaire (SGRQ), mortality, adverse events, and study withdrawal. Probability of withdrawing from the study was 29% greater with tiotropium than salmeterol/fluticasone propionate (P = 0.005). The modeled annual exacerbation rate was 1.28 in the salmeterol/fluticasone propionate group and 1.32 in the tiotropium group (rate ratio, 0.967; 95% confidence interval [CI], 0.836-1.119]; P = 0.656). The SGRQ total score was statistically significantly lower at 2 years on salmeterol/fluticasone propionate versus tiotropium (difference 2.1 units; 95% CI, 0.1-4.0; P = 0.038). Mortality was significantly lower in the salmeterol/fluticasone propionate group; 21 (3%) of patients in this group died compared with 38 (6%) in the tiotropium group (P = 0.032). More pneumonias were reported in the salmeterol/fluticasone propionate group relative to tiotropium (P = 0.008). CONCLUSIONS: We found no difference in exacerbation rate between salmeterol/fluticasone propionate and tiotropium. More patients failed to complete the study while receiving tiotropium. A small statistically significant beneficial effect was found on health status, with an unexpected finding of lower deaths in salmeterol/fluticasone propionate-treated patients. Clinical trial registered with www.clinicaltrials.gov (NCT 00361959).

Long-term erythromycin therapy is associated with decreased chronic obstructive pulmonary disease exacerbations.

RATIONALE: Frequent chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of hospital admission and mortality and are associated with increased airway inflammation. Macrolides have airway antiinflammatory actions and may reduce the incidence of COPD exacerbations. OBJECTIVES: To determine whether regular therapy with macrolides reduces exacerbation frequency. METHODS: We performed a randomized, double-blind, placebo-controlled study of erythromycin administered at 250 mg twice daily to patients with COPD over 12 months, with primary outcome variable being the number of moderate and/or severe exacerbations (treated with systemic steroids, treated with antibiotics, or hospitalized). MEASUREMENTS AND MAIN RESULTS: We randomized 109 outpatients: 69 (63%) males, 52 (48%) current smokers, mean (SD) age 67.2 (8.6) years, FEV1 1.32 (0.53) L, FEV1% predicted 50 (18)%. Thirty-eight (35%) of the patients had three or more exacerbations in the year before recruitment, with no differences between treatment groups. There were a total of 206 moderate to severe exacerbations: 125 occurred in the placebo arm. Ten in the placebo group and nine in the macrolide group withdrew. Generalized linear modeling showed that the rate ratio for exacerbations for the macrolide-treated patients compared with placebo-treated patients was 0.648 (95% confidence interval: 0.489, 0.859; P = 0.003) and that these patients had shorter duration exacerbations compared with placebo. There were no differences between the macrolide and placebo arms in terms of stable FEV1, sputum IL-6, IL-8, myeloperoxidase, bacterial flora, serum C-reactive protein, or serum IL-6 or in changes in these parameters from baseline to first exacerbation over the 1-year study period. CONCLUSIONS: Macrolide therapy was associated with a significant reduction in exacerbations compared with placebo and may be useful in decreasing the excessive disease burden in this important patient population. Clinical trial registered with www.clinicaltrials.gov (NCT 00147667).

COPD exacerbations: defining their cause and prevention.

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.

Airway and systemic inflammation and decline in lung function in patients with COPD.

STUDY OBJECTIVES: Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1. There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1. PATIENTS AND DESIGN: A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8). At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3). RESULTS: During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr. Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 x 10(6) cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05). Patients with frequent exacerbations (> or = 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr). Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018). Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively. CONCLUSIONS: In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function.

Aquaporin-4 immuneglobulin g testing in 36 consecutive jamaican patients with inflammatory central nervous system demyelinating disease.

Epidemiological studies of neuromyelitis optica (NMO) in Jamaica are lacking. Here we reviewed the clinical records of 700 patients undergoing neurological evaluation at the Kingston Public Hospital, the largest tertiary institution in Jamaica over a 4 month period. We investigated the diagnostic utility of Aquaporin-4 ImmuneglobulinG (AQP4-IgG) testing in 36 consecutive patients with a diagnosis of an inflammatory demyelinating disorder (IDD) of the central nervous system (CNS). Patients were classified into 3 categories: i) NMO, n=10; ii) multiple sclerosis (MS), n=14 and iii) unclassified IDD (n=12). All sera were tested for AQP-IgG status by cell binding assay (Euroimmun). No MS cases were positive. Ninety per cent of NMO cases were positive. Four of 12 patients with unclassified IDD tested positive for AQP4-IgG. AQP4-IgG seropositivity was associated with a lower socioeconomic status, higher EDSS (P=0.04) and lower pulmonary function than the seronegative cases (P=0.007). Aquaporin-4 autoimmunity may account for a significant proportion of Jamaican CNS IDDs.

Restrictive pulmonary deficit is associated with inflammation in sub-optimally controlled obese diabetics.

Caribbean data linking inflammation, pulmonary dysfunction and diabetes is unavailable. Spirometry, acanthosis nigricans, hs-CRP were assessed in 109 type 2 diabetics (43% males) mean age=55.6 years, BMI=29.29 kg/m(2), waist circumference=103.86 cm. Residual FEV1/FVC increased with age (P=0.005), BMI (P=0.011) and waist circumference (P=0.003). Residual FVC related inversely to hs-CRP (-0.178), P<0.06) systolic (-0.028, P<0.031), diastolic (-0.247, P<0.010) pressure and weight (-0.25, P<0.009). Residual FEV1 related inversely to diastolic pressure (-0.219, P<0.023), hs-CRP (-0.234, P<0.015), acanthosis nigricans (-0.029, P<0.029). HbA1C and residual FEV1 predict high hs-CRP (P=0.011, P=0.046). Low FVC with inflammation presents in poorly controlled obese diabetics.

Reported pneumonia in patients with COPD: findings from the INSPIRE study.

BACKGROUND: Pneumonia is an important complication of COPD and is reported more often in patients receiving inhaled corticosteroids (ICSs). Little is known about the clinical course and factors predisposing to pneumonia in patients with COPD. We investigated patient characteristics and symptoms occurring before pneumonia reports in the Investigating New Standards for Prophylaxis in Reduction of Exacerbations (INSPIRE) study. METHODS: This was a 2-year, double-blind, double-dummy parallel study of 1,323 patients randomized to salmeterol/fluticasone propionate 50/500 µg bid (SFC) or tiotropium 18 µg once daily (Tio). Baseline demographics, including serum C-reactive protein (CRP) levels, were measured, and daily record cards (DRCs) were completed. RESULTS: We identified 87 pneumonia reports from adverse event records (SFC=62; Tio=25) in 74 patients (SFC=50; Tio=24), compared with 2,255 exacerbations (SFC=1,185; Tio=1,070). Pneumonia was more common in patients with severe dyspnea and in those with a baseline CRP level>10 mg/L. Numbers of de novo pneumonias (events that were not preceded by symptoms of an exacerbation) were similar between treatment groups, but pneumonia was more likely after either a treated or untreated unresolved exacerbation in patients receiving ICSs (SFC=32; Tio=7). Similar results were seen when analysis was confined to radiologically confirmed events. CONCLUSIONS: Pneumonia is much less frequent than exacerbation in COPD. The excess of events with ICS treatment appears to be associated with protracted symptomatic exacerbations. Earlier identification and treatment of these events to prevent pneumonia merits further investigation. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00361959; Study No.: SC040036; URL: clinicaltrials.gov.