Lung function and breathing patterns in hospitalised COVID-19 survivors: a review of post-COVID-19 Clinics.

INTRODUCTION: There is relatively little published on the effects of COVID-19 on respiratory physiology, particularly breathing patterns. We sought to determine if there were lasting detrimental effect following hospital discharge and if these related to the severity of COVID-19. METHODS: We reviewed lung function and breathing patterns in COVID-19 survivors > 3 months after discharge, comparing patients who had been admitted to the intensive therapy unit (ITU) (n = 47) to those who just received ward treatments (n = 45). Lung function included spirometry and gas transfer and breathing patterns were measured with structured light plethysmography. Continuous data were compared with an independent t-test or Mann Whitney-U test (depending on distribution) and nominal data were compared using a Fisher's exact test (for 2 categories in 2 groups) or a chi-squared test (for > 2 categories in 2 groups). A p-value of < 0.05 was taken to be statistically significant. RESULTS: We found evidence of pulmonary restriction (reduced vital capacity and/or alveolar volume) in 65.4% of all patients. 36.1% of all patients has a reduced transfer factor (TLCO) but the majority of these (78.1%) had a preserved/increased transfer coefficient (KCO), suggesting an extrapulmonary cause. There were no major differences between ITU and ward lung function, although KCO alone was higher in the ITU patients (p = 0.03). This could be explained partly by obesity, respiratory muscle fatigue, localised microvascular changes, or haemosiderosis from lung damage. Abnormal breathing patterns were observed in 18.8% of subjects, although no consistent pattern of breathing pattern abnormalities was evident. CONCLUSIONS: An "extrapulmonary restrictive" like pattern appears to be a common phenomenon in previously admitted COVID-19 survivors. Whilst the cause of this is not clear, the effects seem to be similar on patients whether or not they received mechanical ventilation or had ward based respiratory support/supplemental oxygen.

Decreased COPD prevalence in Sweden after decades of decrease in smoking.

BACKGROUND: COPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009. METHODS: Two large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009-2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion. RESULTS: Based on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009-2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking. CONCLUSIONS: The prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.

Impact of gastroesophageal reflux on longitudinal lung function and quantitative computed tomography in the COPDGene cohort.

RATIONALE: Gastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes to the progression of COPD as measured by lung function or computed tomography. OBJECTIVE: To determine the impact of GERD on longitudinal changes in lung function and radiographic lung disease in the COPDGene cohort. METHODS: We evaluated 5728 participants in the COPDGene cohort who completed Phase I (baseline) and Phase II (5-year follow-up) visits. GERD status was based on participant-reported physician diagnoses. We evaluated associations between GERD and annualized changes in lung function [forced expired volume in 1 s (FEV1) and forced vital capacity (FVC)] and quantitative computed tomography (QCT) metrics of airway disease and emphysema using multivariable regression models. These associations were further evaluated in the setting of GERD treatment with proton-pump inhibitors (PPI) and/or histamine-receptor 2 blockers (H2 blockers). RESULTS: GERD was reported by 2101 (36.7%) participants at either Phase I and/or Phase II. GERD was not associated with significant differences in slopes of FEV1 (difference of - 2.53 mL/year; 95% confidence interval (CI), - 5.43 to 0.37) or FVC (difference of - 3.05 mL/year; 95% CI, - 7.29 to 1.19), but the odds of rapid FEV1 decline of ≥40 mL/year was higher in those with GERD (adjusted odds ratio (OR) 1.20; 95%CI, 1.07 to 1.35). Participants with GERD had increased progression of QCT-measured air trapping (0.159%/year; 95% CI, 0.054 to 0.264), but not other QCT metrics such as airway wall area/thickness or emphysema. Among those with GERD, use of PPI and/or H2 blockers was associated with faster decline in FEV1 (difference of - 6.61 mL/year; 95% CI, - 11.9 to - 1.36) and FVC (difference of - 9.26 mL/year; 95% CI, - 17.2 to - 1.28). CONCLUSIONS: GERD was associated with faster COPD disease progression as measured by rapid FEV1 decline and QCT-measured air trapping, but not by slopes of lung function. The magnitude of the differences was clinically small, but given the high prevalence of GERD, further investigation is warranted to understand the potential disease-modifying role of GERD in COPD pathogenesis and progression. CLINICAL TRIALS REGISTRATION: NCT00608764 .

Changes of DNA methylation are associated with changes in lung function during adolescence.

BACKGROUND: Adolescence is a significant period for the gender-dependent development of lung function. Prior studies have shown that DNA methylation (DNA-M) is associated with lung function and DNA-M at some cytosine-phosphate-guanine dinucleotide sites (CpGs) changes over time. This study examined whether changes of DNA-M at lung-function-related CpGs are associated with changes in lung function during adolescence for each gender, and if so, the biological significance of the detected CpGs. METHODS: Genome-scale DNA-M was measured in peripheral blood samples at ages 10 (n = 330) and 18 years (n = 476) from the Isle of Wight (IOW) birth cohort in United Kingdom, using Illumina Infinium arrays (450 K and EPIC). Spirometry was conducted at both ages. A training and testing method was used to screen 402,714 CpGs for their potential associations with lung function. Linear regressions were applied to assess the association of changes in lung function with changes of DNA-M at those CpGs potentially related to lung function. Adolescence-related and personal and family-related confounders were included in the model. The analyses were stratified by gender. Multiple testing was adjusted by controlling false discovery rate of 0.05. Findings were further examined in two independent birth cohorts, the Avon Longitudinal Study of Children and Parents (ALSPAC) and the Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE) cohort. Pathway analyses were performed on genes to which the identified CpGs were mapped. RESULTS: For females, 42 CpGs showed statistically significant associations with change in FEV1/FVC, but none for change in FEV1 or FVC. No CpGs were identified for males. In replication analyses, 16 and 21 of the 42 CpGs showed the same direction of associations among the females in the ALSPAC and BAMSE cohorts, respectively, with 11 CpGs overlapping across all the three cohorts. Through pathway analyses, significant biological processes were identified that have previously been related to lung function development. CONCLUSIONS: The detected 11 CpGs in all three cohorts have the potential to serve as the candidate epigenetic markers for changes in lung function during adolescence in females.

Comparison of pharmacy students' perceptions and attitudes toward spirometry first-hand experience versus paper-based active learning.

BACKGROUND AND PURPOSE: Spirometry is often technically challenging for patients. Previous studies have demonstrated the potential benefits of spirometry in the community pharmacy setting. This study compared pharmacy students' perceptions and attitudes toward performing spirometry, as well as implementing spirometry in clinics and community pharmacies through experiencing spirometry first-hand versus completing paper-based active learning exercises. EDUCATIONAL ACTIVITY AND SETTING: First-year (N = 102) and second-year (N = 70) pharmacy students were provided with the same pre-class materials to learn about the spirometry process. During class, first-year (P1) students performed spirometry tests, while second-year (P2) students completed paper-based active learning exercises about spirometry without performing the test. A survey was provided to each group at the end of the class to: (1) compare students' perception of the difficulty of performing spirometry, and (2) identify patient, clinic, and pharmacy barriers to implementing spirometry testing. FINDINGS: P1 students perceived performing spirometry as significantly more difficult compared to P2 students. Both P1 and P2 students perceived correct posture and breathing technique, and patient discomfort as the most difficult parts of performing spirometry. Significantly more P1 students (91.1%) perceived spirometry as a "helpful and noninvasive tool to screen for pulmonary diseases" than P2 students (54.1%). SUMMARY: Students who experienced spirometry perceived it to be more difficult than those who completed paper-based active learning exercises. Incorporating spirometry into a pharmacy curriculum could be an opportunity to increase students' insight of the difficulty of performing spirometry and their appreciation for the clinical services pharmacists can provide.

Spirometric changes during exacerbations of COPD: a post hoc analysis of the WISDOM trial.

BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with loss of lung function and poor outcomes for patients. However, there are limited data on the time course of changes in forced expiratory volume in 1 s (FEV1) preceding the first reported symptom and after the start of an exacerbation. METHODS: WISDOM was a multinational, randomized, double-blind, active-controlled, 52-week study in patients with severe-to-very severe COPD. Patients received triple therapy (long-acting muscarinic antagonist and long-acting ß2-agonist/inhaled corticosteroid [ICS]) for 6 weeks, and were randomized to continue triple therapy or stepwise withdrawal of the ICS (dual bronchodilator group). After suitable training, patients performed daily spirometry at home using a portable, battery-operated spirometer. In the present post hoc analysis, patients who continued to perform daily home spirometry and completed at least one measurement per week for a 56-day period before and after the start of a moderate or severe exacerbation were included. Missing values were imputed by linear interpolation (intermittent), backfilling (beginning) or carry forward (end). Exacerbation onset was the first day of a reported symptom of exacerbation. RESULTS: Eight hundred and eighty-eight patients in the WISDOM study had a moderate/severe exacerbation after the complete ICS withdrawal visit; 360 of them contributed at least one FEV1 measure per week for the 8 weeks before and after the event and are included in this analysis. Mean daily FEV1 began to decline from approximately 2 weeks before the onset of symptoms of an exacerbation, dropping from 0.907 L (mean Days - 56 to - 36 before the exacerbation) to 0.860 L on the first day of the exacerbation. After the exacerbation, mean FEV1 improved but did not return to pre-exacerbation levels (mean Days 36-56 after the exacerbation, 0.875 L). The pattern of FEV1 changes around exacerbations was similar in the triple therapy and dual bronchodilator groups, and a similar pattern was seen in moderate and severe exacerbations when analysed separately. CONCLUSIONS: Mean lung function starts to decline prior to the first reported symptoms of an exacerbation, and does not recover to pre-exacerbation levels 8 weeks after the event. TRIAL REGISTRATION: WISDOM (ClinicalTrials.gov number, NCT00975195 ).

The effect of changes to GOLD severity stage on long term morbidity and mortality in COPD.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity stage classifies Chronic Obstructive Pulmonary Disease (COPD) into groups based on symptoms, exacerbations and forced expiratory volume in one second (FEV1). This allows patients to change to less severe COPD stages, a novel aspect of assessment not previously evaluated. We aimed to investigate the association between temporal changes in GOLD severity stage and outcomes in COPD patients. METHODS: This was a record-linkage study using patients registered with a Scottish regional COPD network 2000-2015. Annual spirometry & symptoms were recorded and linked to healthcare records to identify exacerbations, hospitalisations and mortality. Spirometry, modified Medical Research Council (mMRC) dyspnoea scale and acute exacerbations over the previous year were used to assign GOLD severity at each visit. A time-dependent Cox model was used to model time to death. Secondary outcomes were respiratory specific mortality and hospitalisations. Effect sizes are expressed as Hazard Ratios HR (95%CI). RESULTS: Four thousand, eight hundred and eighty-five patients (mean age 67.3 years; 51.3% female) with 21,348 visits were included. During a median 6.6 years follow-up there were 1530 deaths. For the secondary outcomes there were 712 respiratory deaths and 1629 first hospitalisations. Across 16,463 visit-pairs, improvement in COPD severity was seen in 2308 (14%), no change in 11,010 (66.9%) and worsening in 3145 (19.1). Compared to patients staying in GOLD stage A, those worsening had a stepwise increased mortality and hospitalisations. CONCLUSIONS: Improving COPD severity classification was associated with reduced mortality and worsening COPD severity was associated with increased mortality and hospitalisations. Change in GOLD group has potential as monitoring tool and outcome measure in clinical trials.

[Personalised COPD care: Where are we going?] / Prise en charge personnalisée de la BPCO, quelles sont les tendances ?

The concept of personalised medicine is recent but the underlying notions are not new: knowing how to adapt care to patients' characteristics is one of the components of the "art of medicine". The advances of science allow to refine considerably the applications of the concept in many fields of medicine including COPD: research has identified phenotypes, endotypes and treatable traits. Personalisation can be applied to all components of care. For instance, the decision to perform screening spirometry relies not only on risk factors (age, smoking, other exposures) but also on symptoms. Assessment of comorbidities often associated with COPD is based on risk factors and their combinations, variable between individuals. Rehabilitation and its components are in essence highly individualised, which a major condition for their success. Last but not least, personalisation of pharmacological therapy, which has long been rather poor, could not benefit from biomarkers of interest (predictive of response), such as blood eosinophil count. Practical strategies using these still need to be established, and new biomarkers may usefully enrich the collection!

Significant predictors of medically diagnosed chronic obstructive pulmonary disease in patients with preserved ratio impaired spirometry: a 3-year cohort study.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition. We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients. METHODS: From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded. The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio <  0.7; n = 687). These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up. RESULTS: COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P <  0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001). PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients. In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors. CONCLUSION: PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function.

Telemedicina, una oportunidad para la espirometría / Telemedicine, an Opportunity for Spirometry

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Science reflects history as society influences science: brief history of "race," "race correction," and the spirometer.

Spirometers are used globally to diagnose respiratory diseases, and most commercially available spirometers "correct" for race. "Race correction" is built into the software of spirometers. To evaluate pulmonary function and to make recordings, the operator must enter the subject's race. In fact, the Joint Working Party of the American Thoracic Society/European Respiratory Society recommends the use of race- and ethnic-specific reference values. In the United States, spirometers apply correction factors of 10-15% for individuals labeled "Black" and 4-6% for people labeled "Asian." Thus race is purported to be a biologically important and scientifically valid category. However, history suggests that race corrections may represent an implicit bias, discrimination, and racism. Furthermore, this practice masks economic and environmental factors. The flawed logic of innate, racial difference is also considered with disability estimates, preemployment physicals, and clinical diagnoses that rely on the spirometer. Thomas Jefferson's Notes on the State of Virginia (1832) may have initiated this mistaken belief by noting deficiencies of the "pulmonary apparatus" of blacks. Plantation physicians used Jefferson's statement to support slavery, believing that forced labor was a way to "vitalize the blood" of deficient black slaves. Samuel Cartwright, a Southern physician and slave holder, was the first to use spirometry to record deficiencies in pulmonary function of blacks. A massive study by Benjamin Apthorp Gould (1869) during the Civil War validated his results. The history of slavery created an environment where racial difference in lung capacity become so widely accepted that race correction became a scientifically valid procedure.

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer.

BACKGROUND: Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients. METHODS: A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO2, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012. RESULTS: Fifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up. CONCLUSIONS: FEV1, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

BACKGROUND: Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). METHODS: To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. RESULTS: Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. CONCLUSION: The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

Favorable longitudinal change of lung function in patients with asthma-COPD overlap from a COPD cohort.

BACKGROUND: The recognition of asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) as a distinct phenotype of COPD or asthma has increased. Although ACO has worse clinical features than non-ACO COPD, limited information is available on long-term outcomes of lung function decline for ACO and non-ACO COPD. METHODS: COPD patients with at least 3 years of follow-up were selected from the Korean Obstructive Lung Disease cohort. ACO was defined based on 3 major criteria: 1) airflow limitation in individuals 40 years of age and older, 2) ≥10 pack-years of smoking history, and 3) a history of asthma or bronchodilator response of > 400 mL in forced expiratory volume in 1 s (FEV1) at baseline; and at least 1 minor criterion: 1) history of atopy or allergic rhinitis, 2) two separated bronchodilator responses of ≥12% and 200 mL in FEV1, or 3) peripheral blood eosinophils ≥300 cells/µL. Lung function decline was compared using a linear mixed effects model for longitudinal data with random intercept and random slope. RESULTS: Among 239 patients, 47 were diagnosed with ACO (19.7%). During the follow-up period, change in smoking status, use of inhaled corticosteroids (ICS) and long-acting ß2-agonists or ICS and at least 2 exacerbations per year were similar between patients with non-ACO COPD and ACO. Over a median follow-up duration of 5.8 years, patients with non-ACO COPD experienced a faster annual decline in pre-bronchodilator FEV1 than patients with ACO (- 29.3 ml/year vs. -13.9 ml/year, P = 0.042), which was persistent after adjustment for confounders affecting lung function decline. CONCLUSION: Patients with ACO showed favorable longitudinal changes in lung function compared to COPD patients over a median follow-up of 5.8 years.

Persistent light to moderate alcohol intake and lung function: A longitudinal study.

Alcohol intake has been inconsistently associated with lung function levels in cross-sectional studies. The goal of our study was to determine whether longitudinally assessed light-to-moderate alcohol intake is associated with levels and decline of lung function. We examined data from 1333 adult participants in the population-based Tucson Epidemiological Study of Airway Obstructive Disease. Alcohol intake was assessed with four surveys between 1972 and 1992. Subjects who completed at least two surveys were classified into longitudinal drinking categories ("never", "inconsistent", or "persistent drinker"). Spirometric lung function was measured in up to 11 surveys between 1972 and 1992. Random coefficient models were used to test for differences in lung function by drinking categories. After adjustment for sex, age, height, education, BMI categories, smoking status, and pack-years, as compared to never-drinkers, persistent drinkers had higher FVC (coefficient: 157 mL, p < 0.001), but lower FEV1/FVC ratio (-2.3%, p < 0.001). Differences were due to a slower decline of FVC among persistent than among never-drinkers (p = 0.003), and these trends were present independent of smoking status. Inconsistent drinking showed similar, but weaker associations. After adjustment for potential confounders, light-to-moderate alcohol consumption was associated with a significantly decreased rate of FVC decline over adult life.

Characterizing undiagnosed chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: A significant proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed. Characterizing these patients can increase our understanding of the 'hidden' burden of COPD and the effectiveness of case detection interventions. METHODS: We conducted a systematic review and meta-analysis to compare patient and disease factors between patients with undiagnosed persistent airflow limitation and those with diagnosed COPD. We searched MEDLINE and EMBASE for observational studies of adult patients meeting accepted spirometric definitions of COPD. We extracted and pooled summary data on the proportion or mean of each risk factor among diagnosed and undiagnosed patients (unadjusted analysis), and coefficients for the adjusted association between risk factors and diagnosis status (adjusted analysis). RESULTS: Two thousand eighty-three records were identified through database searching and 16 articles were used in the meta-analyses. Diagnosed patients were less likely to have mild (v. moderate to very severe) COPD (odds ratio [OR] 0.30, 95%CI 0.24-0.37, 6 studies) in unadjusted analysis. This association remained significant but its strength was attenuated in the adjusted analysis (OR 0.72, 95%CI 0.58-0.89, 2 studies). Diagnosed patients were more likely to report respiratory symptoms such as wheezing (OR 3.51, 95%CI 2.19-5.63, 3 studies) and phlegm (OR 2.16, 95% CI 1.38-3.38, 3 studies), had more severe dyspnea (mean difference in modified Medical Research Council scale 0.52, 95%CI 0.40-0.64, 3 studies), and slightly greater smoking history than undiagnosed patients. Patient age, sex, current smoking status, and the presence of coughing were not associated with a previous diagnosis. CONCLUSIONS: Undiagnosed patients had less severe airflow obstruction and fewer respiratory symptoms than diagnosed patients. The lower disease burden in undiagnosed patients may significantly delay the diagnosis of COPD.

Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

BACKGROUND: Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD). COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments. The differential effects of TS, BS or their combined exposure have not been well characterized yet. This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination. METHODS: Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups. RESULTS: TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01). Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05). CONCLUSIONS: There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures. The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant.

High rates of respiratory symptoms and airway disease in mental health inpatients in a tertiary centre.

BACKGROUND: People with severe mental illness (SMI) have a lower life expectancy due in part to a higher prevalence of cardiac and metabolic disease. Less is known of the prevalence of respiratory disease in this group. AIMS: This cross-sectional, observational study aimed to assess the prevalence of symptoms associated with respiratory disease in patients admitted to an inpatient mental health unit. METHODS: A convenience sample of 82 inpatients had a structured interview and questionnaire completed. The questionnaire included self-reported diagnoses of common diseases and screening questions designed to detect respiratory disease and sleep disordered breathing. Targeted spirometry was performed on the basis of symptoms and smoking status. RESULTS: Patients reported high rates of respiratory symptoms, including wheezing (38%) and dyspnoea (44%); 52% of patients reported daily tobacco use. Productive cough was significantly associated with tobacco use (P < 0.005). Ten patients (18%) had spirometry consistent with chronic obstructive pulmonary disease (COPD) of whom six did not have a formal diagnosis of COPD previously. CONCLUSIONS: People with SMI have high rates of respiratory symptoms with a high prevalence of COPD on spirometry. Half of the COPD cases were not previously diagnosed, suggesting a hidden burden of respiratory disease in patients with SMI.

Frequency and prognostic impact of mid-expiratory flow reduction in stable patients six months after hospitalisation for heart failure with reduced ejection fraction.

AIM: This study investigates the prevalence and prognostic impact of central and small airways obstruction (CAO and SAO) in patients with stable heart failure (HF). METHODS & RESULTS: Spirometry was performed in 585 outpatients (mean age 65±12years, 75% male) six months after hospitalisation for acute decompensation secondary to HF with ejection fraction <40%. We assessed forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and mid-expiratory flow (MEF) at 50% of FVC. CAO was defined by FEV1/FVC <0.7. SAO was defined by FEV1/FVC ≥0.7 plus MEF <60% of predicted value. CAO and SAO were excluded in 359 patients (61% of all). MEF <60% predicted was found in 226 patients (39% of all), among those 88 with CAO (15% of all) and 138 (24% of all) with SAO. During a twelve month follow-up, 42 patients (7.2%) died. Mortality rates of patients with CAO and SAO were comparable (12.5% and 10.9%, respectively, p=0.74), and both higher than in patients without airways obstruction (4.5%, both p<0.01). In univariable Cox regression analysis, both CAO and SAO were associated with 2-fold increased all-cause mortality risk (hazard ratios [95% confidence intervals]: 2.78 [1.33-6.19], p=0.007 and 2.51 [1.24-5.08], p=0.010, respectively). Adjustment for determinants of CAO and SAO, prognostic markers of heart failure and comorbidities attenuated the association of mortality with CAO but not with SAO. CONCLUSIONS: SAO is more common than CAO and indicates an increased mortality risk in HF. Thus, reduced MEF may be a feature of patients at risk and merits special attention in HF management.