Respiratory Medicine: X最新文献

Background

Asthma is a prevalent and potentially life-threatening disease associated with exacerbation and costly hospital admissions. The coagulation cascade is up-regulated in severe asthma and increased fibrinogenesis in the airway may precede exacerbation in moderate asthma.

Objective

A longitudinal prospective study to test the hypothesis that levels of urinary fibrinopeptide A (FP-A), a marker of coagulation, increase prior to an exacerbation of asthma.

Methods

24 non-smoking participants with moderate to severe asthma were recruited and followed to exacerbation and to recovery for up to 8 weeks afterwards. Baseline measurements included spirometry, full blood count, atopic status and plasma markers of coagulation. Participants provided daily Peak Expiratory Flow (PEF) readings and three urine samples per week for analysis of FP-A, a specific marker of activation of coagulation. A novel method to concentrate urinary FP-A for immunodetection and quantification was developed. Participants were followed up until exacerbation, when baseline measurements were repeated, and monthly thereafter for 2 months or to recovery.

Measurements and main findings

17 participants exacerbated during the study. Significantly increased concentrations of plasma D-dimer (0.25(0.2–0.42) vs 0.21(0.12–0.29) μg FEU/ml, p = 0.02) were found at exacerbation. A peak in urinary FP-A concentration was detected on average 4.2 ± 2 days prior to exacerbation and was significantly (p < 0.05) higher than at exacerbation or 7 days later. Urinary FP-A concentrations correlated positively with time to recovery and negatively (p < 0.01) with IgE concentration.

Conclusion

FP-A is detectable in urine several days before the onset of an asthma exacerbation indicating disordered coagulation preceding asthma exacerbations.

Study objectives

A) Compare the standard obstructive sleep apnea (OSA) screening instruments to each other and to the judgement of experienced sleep clinicians. B) Evaluate if a novel OSA screening instrument constructed from components of the standard OSA screening instruments would improve the accuracy of screening.

Methods

We screened 344 subjects using the most commonly used OSA screening instruments- Berlin sleep questionnaire, STOP, STOP-BANG, Mallampati upper airway score and Epworth sleepiness scale. A clinical impression score (CIS) reflected the clinician's likelihood of OSA being present. All subjects underwent nocturnal polysomnography. The sensitivity and specificity of all screening instruments and the CIS for any OSA and for moderate-to-severe OSA were calculated. We constructed a logistic regression model incorporating all the components of these OSA screening instruments in an effort to develop a more accurate OSA screening metric.

Results

STOP-BANG was the most sensitive instrument (sensitivity of 93% and 97% for any OSA and moderate-to-severe OSA respectively). Its ability to exclude OSA was on par with the CIS (sensitivity of 95% and 97% respectively). The logistic regression model incorporating all the individual items of the OSA screening instruments did not meaningfully improve accuracy.

Conclusions

A comprehensive clinical evaluation and STOP-BANG both possess sufficiently high sensitivity to be useful screening tools. Combining the existing OSA screening instruments into a single instrument did not appreciably improve upon the accuracy of the STOP-BANG. Further refinements of the existing OSA screening instruments would require identifying new, easily recognizable risk factors.

Objectives

To estimate treatment- and productivity-related costs associated with COPD in two different samples, and to analyse the association between the costs and moderate and severe exacerbations.

Methods

We performed a baseline visit and four telephone-interviews during a one-year follow-up of 81 COPD cases and 132 controls recruited from a population-based sample, and of 205 hospital-recruited COPD patients. COPD was defined by post-bronchodilator spirometry. Total costs consisted of treatment related costs and costs of productivity losses. Exacerbation-related costs were estimated by multivariate median regression.

Results

The average annual disease-related costs for a COPD patient from the hospital sample was nearly twice as high as for a COPD case from the population sample (€26,518 vs €15,021), and nearly four times as high as for a control subject (€6740). For both sampling sources, the average annual costs of productivity losses were substantially higher than the treatment related costs (€17,014 vs €9,504, €11,192 vs €3,829, and €4494 vs €2,246, for the hospital COPD patients, the population-based COPD cases, and the controls, respectively). Severe exacerbations were an important cost driver for the treatment related costs in both COPD groups. Moderate exacerbations explained all the costs of productivity losses in the population-based COPD cases, but did not affect the costs of productivity losses in the hospital-recruited COPD patients.

Conclusion

We found that there were significant incremental costs associated with COPD, and the treatment related costs were significantly affected by exacerbations. The costs of productivity losses substantially exceeded the treatment related costs in both sampling sources.

As Covid-19 affects millions of people worldwide, the global health care will encounter an increasing burden of the aftermaths of the disease. Evidence shows that up to a fifth of the patients develop fibrotic tissue in the lung. The SARS outbreak in the early 2000 resulted in chronic pulmonary fibrosis in a subset (around 4%) of the patients, and correlated to reduced lung function and forced expiratory volume (FEV). The similarities between corona virus infections causing SARS and Covid-19 are striking, except that the novel coronavirus, SARS-CoV-2, has proven to have an even higher communicability. This would translate into a large number of patients seeking care for clinical signs of pulmonary fibrosis, given that the Covid-19 pandemic has up till now (Sept 2020) affected around 30 million people. The SARS-CoV-2 is dependent on binding to the angiotensin converting enzyme 2 (ACE2), which is part of the renin-angiotensin system (RAS). Downregulation of ACE2 upon virus binding disturbs downstream activities of RAS resulting in increased inflammation and development of fibrosis. The poor prognosis and risk of developing pulmonary fibrosis are therefore associated with the increased expression of ACE2 in risk groups, such as obesity, heart disorders and aging, conferring plenty of binding opportunity for the virus and subsequently the internalization of ACE2, thus devoiding the enzyme from acting counter-inflammatory and antifibrotic. Identifying pathways that are associated with Covid-19 severity that result in pulmonary fibrosis may enable early diagnosis and individualized treatment for these patients to prevent or reduce irreversible fibrotic damage to the lung.

Background and objective

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by a progressive loss of lung function, a restrictive ventilatory impairment, and a high five-year mortality. Our aim was to characterize clinical features of IPF at baseline and to assess which of those that would predict mortality.

Methods

We used baseline data at inclusion collected from the Swedish IPF registry between January 2014 and October 2018. Patients were followed for at least six months. Demographics, lung function (forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity of carbon monoxide (DLCO%)), 6-min walking test (6MWT), lowest oxygen saturation during 6MWT (L-SpO₂), King's brief interstitial lung disease health status questionnaire (K-BILD) scores were collected. GAP index and Charlson Comorbidity Index (CCI) were calculated. Transplant-free survival was registered during the follow-up time.

Results

Two hundred and twenty patients were included in the study. Fifty-seven (26%) died and six (3%) underwent lung transplant during a mean follow-up time of 24 months. Out of 220 patients, 63 patients (29%) had a FVC% equal or over 80% of predicted at baseline. Only 17 out of 155 (11%) patients had a normal TLC%. Walking distance during a 6MWT was an independent predictor of outcome death/transplant (HR 0.80, 95%CI 0.65–0.99, p = 0.037), when adjusted for TLC%, K-BILD and GAP stage in a multivariate cox regression model.

Conclusion

Our results confirm the relevance of the 6MWT as main predictor of mortality at diagnosis in IPF patients.

Bronchiectasis should be considered in anyone with chronic cough and sputum production. High resolution CT is the diagnostic test of choice for diagnosis of bronchiectasis, showing dilated non-tapering bronchi especially into the peripheral lung, increased ratio of the bronchial:arterial diameters, and occasionally mucous plugs within the dilated bronchi. Once a diagnosis of bronchiectasis is made, clinicians must determine whether workup for a predisposing cause is necessary and what diagnostic tests to obtain. Herein, we provide a brief synopsis of the known causes of bronchiectasis with a primary focus on the diagnostic tests that can help uncover an underlying vulnerability to bronchiectasis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease that kills as many Americans as breast cancer each year. This study investigated whether lung function decline and survival associates with adaptive immunity in patients with IPF, specifically the expression of checkpoint molecules ICOS, CD28 and PD-1 on circulating CD4 T cells. Clinical data, blood samples and pulmonary function tests were collected prospectively and longitudinally from 59 patients with IPF over a study period of 5 years. Patients were followed until death, lung transplantation, or study end, and cell surface expression of CD45RO, CD28, ICOS, and PD-1 was measured on CD4 T cells via flow cytometry. Repeated measures of ICOS and CD28 on CD4 T cells revealed significant associations between declining ICOS and CD28 expression, and declining lung function parameters FVC and DLCO, independent of age, sex, race, smoking history, or immunosuppressant use. Strikingly, patients in the highest quintile of ICOS at study entry had markedly improved survival, while those with low CD28 fared poorly. No change in PD-1 expression was found. Analysis of ICOS and CD28 from the first blood draw identified three populations of IPF patients; those at high risk for early death, those with intermediate risk, and those at low risk. These results highlight the role of T cell mediated immunity in IPF survival, finding the assessment of two T cell stimulatory checkpoint molecules, CD28 and ICOS, was sufficient to discriminate three distinct survival trajectories over 5 years of patient follow up.

Objectives

The clinical benefit of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily budesonide/formoterol (BUD/FOR) for patients with symptomatic chronic obstructive pulmonary disease (COPD) was demonstrated in a clinical trial setting (FULFIL [NCT02345161]). The lifetime cost-effectiveness analysis of FF/UMEC/VI versus BUD/FOR, based on FULFIL data, is reported here.

Methods

A previously developed and validated GALAXY-COPD linked-risk equation model was used to assess the cost-effectiveness of FF/UMEC/VI from the UK National Health Service (NHS) perspective. Baseline characteristics and efficacy results from FULFIL and UK NHS reference cost data (2017) were included as inputs. Exacerbation rates (undiscounted), costs, life years (LYs; undiscounted) and quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were calculated over a lifetime horizon. Costs and QALYs were discounted at 3.5% per year, beyond one year, in accordance with National Institute for Health and Care Excellence (NICE) guidelines. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results.

Results

Predicted cumulative exacerbations per patient over a lifetime were 8.393 with FF/UMEC/VI and 10.456 with BUD/FOR. Patients receiving FF/UMEC/VI gained an additional 0.764 LYs and 0.492 QALYs, at an additional mean cost of £1,652, resulting in an ICER of £3,357 per QALY gained (95% confidence interval: £1,816, £5,194) compared with BUD/FOR. The ICER remained below £6,000 in all but one of the scenario and sensitivity analyses.

Conclusions

Compared with BUD/FOR, treatment with FF/UMEC/VI was predicted to improve health outcomes at an additional cost that suggests it would be cost-effective for patients with COPD in the UK.

Objective

We examined the association between blood eosinophil levels and subsequent rate of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in a population-based cohort of COPD patients managed in primary care.

Methods

This retrospective cohort study included COPD patients from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics. Patients had ≥1 blood eosinophil count that was not performed within ±30 days of an AECOPD episode. Blood eosinophil counts were modelled as a continuous exposure variable using a fractional polynomial model; the best fitting model was plotted against the incidence rate (IR) of moderate or severe AECOPD per person-year (PY), stratified by AECOPD history and inhaled corticosteroid (ICS) use.

Results

A total of 17,495 patients were included. In the overall cohort, the adjusted IRs of moderate or severe AECOPD increased modestly with increasing eosinophil counts, from 0.80/PY for blood eosinophil levels <100 cells/μL to 0.93/PY for 700 + cells/μL. Adjusted IRs for moderate or severe AECOPD were higher for those with a history of moderate or severe AECOPD, and increased with increasing blood eosinophil levels compared with those with no prior history of AECOPD. Treatment with ICS was associated with higher IRs of moderate or severe AECOPD, which increased with increasing blood eosinophil levels compared with non-exposure to ICS.

Conclusion

History of AECOPD and ICS use appear associated with the impact of blood eosinophil levels on the rate of AECOPD, and are important considerations for future studies exploring the relationship between blood eosinophil levels and AECOPD risk.