The association between frailty and survival in patients with pleural disease: a retrospective cohort study.

BACKGROUND: There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease. METHODS: In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2). RESULTS: 676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161-1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02-2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24-2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17-8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01-18.01, p < 0.0001). CONCLUSION: This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients' frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management. TRIAL REGISTRATION: This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Nosocomial COVID-19 infection: examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople).

BACKGROUND: Hospital admissions for non-coronavirus disease 2019 (COVID-19) pathology have decreased significantly. It is believed that this may be due to public anxiety about acquiring COVID-19 infection in hospital and the subsequent risk of mortality. AIM: To identify patients who acquire COVID-19 in hospital (nosocomial COVID-19 infection (NC)) and their risk of mortality compared to those with community-acquired COVID-19 (CAC) infection. METHODS: The COPE-Nosocomial Study was an observational cohort study. The primary outcome was the time to all-cause mortality (estimated with an adjusted hazard ratio (aHR)), and secondary outcomes were day 7 mortality and the time-to-discharge. A mixed-effects multivariable Cox's proportional hazards model was used, adjusted for demographics and comorbidities. FINDINGS: The study included 1564 patients from 10 hospital sites throughout the UK, and one in Italy, and collected outcomes on patients admitted up to April 28th, 2020. In all, 12.5% of COVID-19 infections were acquired in hospital; 425 (27.2%) patients with COVID died. The median survival time in NC patients was 14 days compared with 10 days in CAC patients. In the primary analysis, NC infection was associated with lower mortality rate (aHR: 0.71; 95% confidence interval (CI): 0.51-0.98). Secondary outcomes found no difference in day 7 mortality (adjusted odds ratio: 0.79; 95% CI: 0.47-1.31), but NC patients required longer time in hospital during convalescence (aHR: 0.49, 95% CI: 0.37-0.66). CONCLUSION: The minority of COVID-19 cases were the result of NC transmission. No COVID-19 infection comes without risk, but patients with NC had a lower risk of mortality compared to CAC infection; however, caution should be taken when interpreting this finding.

How much do GOLD stages reflect CT abnormalities in COPD patients?

PURPOSE: Severity of chronic obstructive pulmonary disease (COPD) can be graded using the classification released in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report. Such classification is essentially based on spirometry and does not recognise the role of other measures. The aim of this study was to assess whether the GOLD stages correlate with the extent of pulmonary emphysema and other ancillary computed tomography CT features in a population of smokers with stable COPD. MATERIALS AND METHODS: Based on clinical assessment and lung-function testing, patients were classified according to the GOLD criteria. CT scans were visually evaluated for extent of emphysema and airway abnormalities. RESULTS: A total of 43 patients were enrolled. The amount of emphysema was described as minimal in six patients with stage 0, and as moderate in seven patients with stage 0. In stages I and II, the extent of emphysema ranged from minimal to severe, whereas we observed the presence of severe emphysema in most patients in stages III and IV. According to the regression model, only CT emphysema extent independently predicted the GOLD stage (r2 = 0.58; p < 0.001). The cutoff value of emphysema extent of 31.5% allowed us to distinguish patients with a GOLD stage > or = III. CONCLUSIONS: Although we found a significant correlation between CT emphysema extent and GOLD stages, different percentage of emphysema extent can be observed among each GOLD stage. The upper limit of 31.5% of emphysema extent may indicate a boundary for a clinically worsening status.

Microsatellite analysis of induced sputum DNA in patients with lung cancer in heavy smokers and in healthy subjects.

Abnormality in the fragile histidine triade (FHIT), a candidate tumor suppressor gene located in chromosome region 3 (3p14.2), has been frequently found in multiple tumor types, including lung cancer. In this study, the authors assessed the consistency of DNA microsatellite analysis of induced sputum (IS), as compared to that of blood and plasma. They also evaluated the loss of heterozigosity (LOH) and microsatellite instability (MSI) in 3 different loci, D3S1300, D3S1313, and D3S1234, all internal to the FHIT gene, in IS, blood, and plasma from patients with lung cancer, smokers, and healthy subjects. Eighteen patients with lung cancer (3 females, age mean +/- SD: 63 +/- 7 years), 39 smokers (23 females, age mean +/- SD: 57 +/- 6 years and cigarette pack-years mean +/- SD: 34 +/- 12), and 22 healthy nonsmoking subjects (13 females, age mean +/- SD: 63 +/- 5 years) were studied. DNA was extracted from blood, plasma, and IS, by means of a standard method. Analysis of LOH and MSI were performed using a fluorescent polymerase chain reaction (PCR)-based approach, followed by capillary electrophoresis. The ratios between the peak heights (phs), expressed as random fluorescence units, from plasma/blood (p/b) and induced sputum/blood (is/b) in all three loci were considered. The biases (agreement limits) between the mean ph ratio from p/b and is/b of D3S1300, D3S1313, and D3S1234 were respectively 0.07 (- 0.39 to 0.53), 0.016 (- 0.32 to 0.35), - 0.10 (- 0.51 to 0.30) in the patients; - 0.04 (- 0.52 to 0.43), - 0.06 (- 0.31 to 0.18), - 0.08 (- 0.48 to 0.30) in smokers; and - 0.11 (- 0.40 to 0.17), - 0.05 (- 0.53 to 0.43), - 0.09 (- 0.51 to 0.33) in healthy subjects. LOH and MSI in at least one locus were observed in 55% of patients, in 18% of smokers, and in 4.5% of healthy subjects (P < 0.001). These results showed that IS DNA provided data that were consistent with those from blood and plasma. These findings highlight new prospects for early tumor detection by a noninvasive technique based on the analysis of genetic alterations in induced sputum.

High resolution CT (HRCT) of the lung in adults. Defining the limits between normal and pathologic findings.

Under normal conditions, HRCT shows secondary lobule structures and allows for a precise evaluation, with inspiratory and expiratory scans, of central airways dimensions, lung area and parenchymal density. Frequently, asymptomatic smokers with normal lung function tests, present with mild abnormalities not visible at chest X-ray: bronchial thickening, bronchiolectasis, respiratory bronchiolitis and centrilobular or paraseptal emphysema. In the elderly, HRCT studies often show borderline findings such as age-related tracheo-bronchial calcifications and emphasise the progressive increase in the bronchoarterial ratio. Another frequent finding is expiratory air trapping, which can be associated with a variety of lung diseases, but can also represent a physiologic and temporary finding, during an episode of sub-clinical bronchospasm or related to local variation of bronchiolar dynamic compliance. The knowledge of the boundaries between normality and pathology is an essential prerequisite for the correct interpretation HRCT findings.

Early smoking-induced lung lesions in asymptomatic subjects. Correlations between high resolution dynamic CT and pulmonary function testing.

PURPOSE: To evaluate the prevalence and significance of the pathological effects of cigarette smoking on the lung and the sensitivity of high-resolution CT (HRCT) in the recognition of early smoking-induced lesions in asymptomatic former or current smokers. MATERIALS AND METHODS: We performed a prospective and consecutive analysis of 36 volunteers (16 males, 20 females), 10 non-smokers (3 males; 7 females) and 26 smokers (13 males; 13 females / 17 current smokers; 9 former smokers), all asymptomatic and with normal respiratory flows. These subjects underwent lung function testing and HRCT, after providing written informed consent for the study. The HRCT scans were obtained at three pre-selected levels (aortic arch, tracheal carina and venous hilum). The same scans were obtained in post-expiration phase. At the level of the apical segmental bronchus of the right upper lobe, we measured on the monitor wall thickening, and the total and internal diameters using the techniques reported in literature. Each study was independently evaluated by two radiologists that were blinded to all clinical and functional data; they also evaluated the presence, prevalence and type of emphysema, areas of patchy hyperlucency and oligoemia in the inspiration phase and areas of expiratory air trapping. The extension was evaluated with the visual score method. The data obtained were analysed with the Windows SPSS package for statistical analysis. RESULTS: The two groups (non smokers and smokers) showed significant differences in some functional tests such as FEV1 (p<0.005) and Tiffeneau index (p<0.005), which were lower in current-smokers or former-smokers, although still within the normal range. The HRCT study did not show areas of emphysema or air trapping in non smokers. In the smokers' group, air trapping was observed in 30.7% of cases: 33.3% former-smokers and 29.4% current smokers (mean extension was 21.36% in former smokers and 9.48% in current smokers). Mean extension in the smokers' group was 13.94%. Pulmonary emphysema was found in 34.6% of cases in the smokers' group: 33.3% former-smokers and 35.2% current-smokers. Emphysema was prevalent in the upper lobes (88.8%). Mean extension was 8.76% in the former smokers group and 18.81% in current-smokers, with a total mean extension of 15.47% in the smokers' group. Statistically, there was a significant difference between non-smokers and smokers as regards emphysema extension and expiratory air trapping (p=0.034 and p=0.050, respectively). The smokers' group had a significantly wider diameter of the apical segmental bronchus of the right upper lobe than the controls. There was no significant statistical correlation between this dilatation and the emphysema score (r=0.051; p=0.81). The entity of smoking history did not correlate with emphysema extension or air trapping or with the size of the apical segmental bronchus of the right upper lobe. CONCLUSIONS: Our study demonstrates that HRCT is more sensitive and specific than commonly-used functional tests for the evaluation of initial emphysema in asymptomatic smokers. We observed expiratory air trapping only in the smokers' group, and only of the lobular type, without evidence of disease in inspiratory scans. Among the smokers and former-smokers, air trapping was found in 30.7% of subjects, with a mean extension lower than 10%. Our results therefore suggest that, even in asymptomatic subjects, expiratory air trapping is probably pathological and, once bronchial asthma has been excluded, it may be related to cigarette smoking and indicate early inflammatory bronchiolar damage. HRCT may therefore be regarded as a useful tool in the early diagnosis of smoking-related lung disease.

Air pollution and reversible chronic respiratory diseases.

Air pollution is one of the world's most serious environmental problems. It has been common knowledge for many years now that the lung is one of the main target organs of environmental agents. Over the last ten years, in particular, lung diseases have increased dramatically and the literature on the subject reports high death rates from lung cancer and an increased incidence of bronchial asthma and chronic obstructive pulmonary disease (COPD). These respiratory diseases are also caused by exposure to environmental agents, especially air pollution. Outdoor pollution is related to many compounds and, in assessing the air-borne pollutants and their association with respiratory damage, the role of particulate matter (PM) is of major importance. In addition to outdoor pollution, indoor pollution also exists and consists of environmental substances usually found outside which enter the internal environment, and/or of locally produced substances. Air pollution exposure involves the contact of pollutants with the respiratory tract, such exposure being measured according to two parameters: intensity and duration. Generally speaking, the pathogenic effects of environmental pollution on the organism fall into two categories: acute, or short-term effects, and long-term effects, depending on the time required from exposure to the manifestation of its effect. Short-term effects consist of irritant symptoms affecting the airways with different degrees of severity, while long-term effects, related to chronic exposure, are associated with chronic respiratory diseases, and unremitting symptoms such as coughing, wheezing, etc. Moreover, air irritants can give rise to inflammatory damage of the mucous membrane of the airways, thereby making it more susceptible to various types of allergens. In conclusion, air pollution is an important etiological factor for many chronic respiratory disorders, such as bronchial asthma and COPD. Prevention programs and early treatments are essential in an attempt to block the clinical-functional deterioration caused by these respiratory diseases.

[Educational programs and self-management in bronchial asthma]. / Programmi educazionali e self-management nell'asma bronchiale.

Bronchial asthma is one of the most common chronic diseases in the world and can affect people of all ages. In the last few years there has been a considerable improvement in the etiopathogenetic knowledge of the disease and extremely effective anti-asthmatic drugs are available. However, asthma-related morbidity and mortality are increased, especially in Western countries. In an attempt to reverse this negative trend, for a number of years national and international guidelines on asthma have been published all over the world. These guidelines have the aim of improving asthma diagnosis and treatment and of conveying a fundamental educational message both to health workers and to patients and their families. From the data in the literature it can be clearly seen that only through the application of valid educational programs is it possible for asthmatics to improve their knowledge of the disease and to understand how they can look after themselves by a careful evaluation of their own symptoms and respiratory function. They should also be aware of the drugs available for the treatment of both acute asthmatic crises and chronic asthma, but especially of the fact that this chronic inflammatory affection can be fully treated. In particular, an educational program organized with groups of maximum 10-12 people attending 2 lessons and with helpful training tools, can increase significantly asthma knowledge, treatment compliance and patient self-management. The aim of this review is to highlight the importance of educational programs and those obscure areas which slow down their large scale application and universal acceptance.