Non-invasive testing for liver pathology in alpha-1 antitrypsin deficiency.

BACKGROUND: Many patients with alpha-1 antitrypsin deficiency (A1ATD) receive care in respiratory clinics without access to specialist hepatology expertise. Liver disease can develop asymptomatically, and non-invasive markers of fibrosis may help identify patients who require definitive assessment with liver biopsy. We evaluated the utility of non-invasive markers of liver fibrosis in A1ATD to guide testing in settings without ready access to hepatology expertise. METHODS: Patients attending the London A1ATD service undergo assessment using blood tests to calculate the 'APRI' and 'FIB-4' score, liver ultrasound and Fibroscan. Liver biopsy is offered to patients who have abnormal liver function tests with abnormal liver ultrasound and/or liver stiffness >6 kPa on Fibroscan. Liver biopsies were assessed for the presence of A1AT, steatosis, fibrosis and inflammation. RESULTS: 75 patients with A1ATD had results for analysis, 56% were female, age 16-82 years. 75% of patients had Fibroscan <6 kPa, 19% had Fibroscan 6-7.9 kPa and 6%>8 kPa. There was a significant correlation between FIB-4 and Fibroscan (r=0.244, p=0.035). Fibroscan >6 kPa corresponded to a FIB-4 score of >1.26. However, FIB-4 >1.26 had poor sensitivity (47%), specificity (32%) and positive-predictive value (PPV; 36%) to identify Fibroscan >6 kPa. The negative-predictive value (NPV) was stronger at 81%. APRI data were similar. Twelve patients underwent liver biopsy, with 11 reports available for analysis. Six had FIB-4 scores<1.26 and five had Fibroscan of <6 kPa. A1AT was present in 64% of biopsies, steatosis in 82%, mild fibrosis in 36%, moderate fibrosis in 9% and severe fibrosis in 9%. CONCLUSION: A combination of liver ultrasound and non-invasive fibrosis tests can help identify patients with A1ATD liver injury. However, APRI and FIB-4 scores alone had poor sensitivity and specificity to justify use as an independent tool for liver pathology in A1ATD.

Once Daily Versus Overnight and Symptom Versus Physiological Monitoring to Detect Exacerbations of Chronic Obstructive Pulmonary Disease: Pilot Randomized Controlled Trial.

BACKGROUND: Earlier detection of chronic obstructive pulmonary disease (COPD) exacerbations may facilitate more rapid treatment with reduced risk of hospitalization. Changes in pulse oximetry may permit early detection of exacerbations. We hypothesized that overnight pulse oximetry would be superior to once-daily monitoring for the early detection of exacerbations. OBJECTIVE: This study aims to evaluate whether measuring changes in heart rate and oxygen saturation overnight is superior to once-daily monitoring of both parameters and to assess symptom changes in facilitating earlier detection of COPD exacerbations. METHODS: A total of 83 patients with COPD were randomized to once-daily or overnight pulse oximetry. Both groups completed the COPD assessment test questionnaire daily. The baseline mean and SD for each pulse oximetry variable were calculated from 14 days of stable monitoring. Changes in exacerbation were expressed as Z scores from this baseline. RESULTS: The mean age of the patients was 70.6 (SD 8.1) years, 52% (43/83) were female, and the mean FEV1 was 53.0% (SD 18.5%) predicted. Of the 83 patients, 27 experienced an exacerbation. Symptoms were significantly elevated above baseline from 5 days before to 12 days after treatment initiation. Day-to-day variation in pulse oximetry during the stable state was significantly less in the overnight group than in the once-daily group. There were greater relative changes at exacerbation in heart rate than oxygen saturation. An overnight composite score of change in heart rate and oxygen saturation changed significantly from 7 days before initiation of treatment for exacerbation and had a positive predictive value for exacerbation of 91.2%. However, this was not statistically better than examining changes in symptoms alone. CONCLUSIONS: Overnight pulse oximetry permits earlier detection of COPD exacerbations compared with once-daily monitoring. Monitoring physiological variables was not superior to monitoring symptoms, and the latter would be a simpler approach, except where there is a need for objective verification of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03003702; https://clinicaltrials.gov/ct2/show/NCT03003702.

Enrichment of the airway microbiome in people living with HIV with potential pathogenic bacteria despite antiretroviral therapy.

BACKGROUND: Long-term antiretroviral therapy (ART) enables people living with HIV (PLW-HIV) to be healthier and live longer; though they remain at greater risk of pneumonia and chronic lung disease than the general population. Lung microbial dysbiosis has been shown to contribute to respiratory disease. METHODS: 16S-rRNA gene sequencing on the Miseq-platform and qPCR for typical respiratory pathogens were performed on sputum samples collected from 64 PLW-HIV (median blood CD4 count 676 cells/µL) and 38 HIV-negative participants. FINDING: Richness and α-diversity as well as the relative-abundance (RA) of the major taxa (RA>1%) were similar between both groups. In unweighted-Unifrac ß-diversity, the samples from PLW-HIV showed greater diversity, in contrast to the HIV negative samples which clustered together. Gut bacterial taxa such as Bilophila and members of Enterobacteriaceae as well as pathogenic respiratory taxa (Staphylococcus, Pseudomonas and Klebsiella) were significantly more frequent in PLW-HIV and almost absent in the HIV-negative group. Carriage of these taxa was correlated with the length of time between HIV diagnosis and initiation of ART (Spearman-rho=0·279, p=0·028). INTERPRETATION: Although the core airway microbiome was indistinguishable between PLW-HIV on effective ART and HIV-negative participants, PLW-HIV's respiratory microbiome was enriched with potential respiratory pathogens and gut bacteria. The observed differences in PLW-HIV may be due to HIV infection altering the local lung microenvironment to be more permissive to harbour pathogenic bacteria that could contribute to respiratory comorbidities. Prompt start of ART for PLW-HIV may reduce this risk.

The effect of HIV status on the frequency and severity of acute respiratory illness.

INTRODUCTION: Antiretroviral therapy has improved the health of people living with HIV (PLW-HIV), though less is known about how this impacts on acute respiratory illness. These illnesses are a common cause of ill health in the general population and any increase in their frequency or severity in PLW-HIV might have significant implications for health-related quality of life and the development of chronic respiratory disease. METHODS: In a prospective observational cohort study following PLW-HIV and HIV negative participants for 12 months with weekly documentation of any acute respiratory illness, we compared the frequency, severity and healthcare use associated with acute respiratory illnesses to determine whether PLW-HIV continue to have a greater frequency or severity of such illnesses despite antiretroviral therapy. RESULTS: We followed-up 136 HIV positive and 73 HIV negative participants for 12 months with weekly documentation of any new respiratory symptoms. We found that HIV status did not affect the frequency of acute respiratory illness: unadjusted incidence rates per person year of follow-up were 2.08 illnesses (95% CI 1.81-2.38) and 2.30 illnesses (1.94-2.70) in HIV positive and negative participants respectively, IRR 0.87 (0.70-1.07) p = 0.18. However, when acute respiratory illnesses occurred, PLW-HIV reported more severe symptoms (relative fold-change in symptom score 1.61 (1.28-2.02), p <0.001) and were more likely to seek healthcare advice (42% vs 18% of illnesses, odds ratio 3.32 (1.48-7.39), p = 0.003). After adjustment for differences in baseline characteristics, PLW-HIV still had higher symptom scores when unwell. CONCLUSIONS: HIV suppression with antiretroviral therapy reduces the frequency of acute respiratory illness to background levels, however when these occur, they are associated with more severe self-reported symptoms and greater healthcare utilisation. Exploration of the reasons for this greater severity of acute respiratory illness may allow targeted interventions to improve the health of people living with HIV. TRIAL REGISTRATION: ISRCTN registry (ISRCTN38386321).

IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial.

INTRODUCTION: Compared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease. METHODS AND ANALYSIS: This study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis. ETHICS AND DISSEMINATION: This study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN95243114 SECONDARY IDENTIFYING NUMBERS: University College London/University College London Hospitals Joint Research Office 17/0726.National Institute for Health Research, UK 16/88/06.

Systematic identification and referral of smokers attending HIV ambulatory care highlights the failure of current service provision in an at-risk population.

Introduction: People living with HIV (PLWH) are more likely to smoke than the general population and are at greater risk of smoking-related illness. Healthcare services need to address this burden of preventable disease. Methods: We evaluated the impact of a brief intervention that asked service users about smoking when they attended for ambulatory HIV care in London, UK, and offered referral to smoking cessation. Results: Overall, 1548 HIV-positive individuals were asked about their smoking status over a 12-month period. Of this group, 385 (25%) reported that they were current smokers, 372 (97%) were offered referral to smoking cessation services and 154 (40%) accepted this. We established an outcome of referral for 114 (74%) individuals. A total of 36 (10% of smokers) attended stop smoking clinics and 16 (4%) individuals were recorded as having quit smoking. Discussion: The simple intervention of asking PLWH about tobacco smoking and offering referral to smoking cessation services rapidly identified current smokers, 40% of whom accepted referral to smoking cessation services. This highlights the importance of promoting behaviour and lifestyle changes with every contact with health services. However, a large proportion of those referred were either not seen in local services or the outcome of referral could not be ascertained. If the risk of smoking-related morbidity among PLWH is to be reduced, more sustainable referral pathways and ways of improving uptake of smoking cessation services must be developed.

Global use, utility, and methods of tele-health in COPD: a health care provider survey.

Introduction: Advances in technology offer various solutions that might help optimize the care provided to patients living with chronic non-communicable diseases such as chronic obstructive pulmonary disease (COPD). However, the efficacy of tele-health in COPD is still controversial. Despite this, there appears to be widespread adoption of this technology. Aim: To explore the international use of tele-heath for COPD, to assess the perceptions of clinicians employing tele-health in COPD, and to summarize the techniques that have been used by health care providers to personalize alarm limits for patients with COPD enrolled on tele-health programs. Methods: A cross-sectional survey consisting of 15 questions was distributed and advertised to health care professionals worldwide. Questions were designed to cover five different aspects of tele-health in COPD: purpose of use, equipment type, clinician perceptions, variables monitored, and personalization of alarm limits. Results: A total of 138 participants completed the survey from 29 different countries. As high as 59% of the participants had ever used tele-health for COPD, and 33% still provided tele-health services to patients with COPD. Tele-health was most commonly used for baseline monitoring, with 90% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate, and the use of rescue medication. Conclusion: Twenty-nine different countries use tele-health for managing COPD and therefore there is widespread international use of tele-health in COPD. The majority of providers thought tele-health was effective despite evidence to the contrary.

Use, utility and methods of telehealth for patients with COPD in England and Wales: a healthcare provider survey.

Introduction: Although the effectiveness of domiciliary monitoring (telehealth) to improve outcomes in chronic obstructive pulmonary disease (COPD) is controversial, it is being used in the National Health Service (NHS). Aim: To explore the use of teleheath for COPD across England and Wales, to assess the perceptions of clinicians employing telehealth in COPD and to summarise the techniques that have been used by healthcare providers to personalise alarm limits for patients with COPD enrolled in telehealth programmes. Methods: A cross-sectional survey consisting of 14 questions was sent to 230 COPD community services in England and Wales. Questions were designed to cover five aspects of telehealth in COPD: purpose of use, equipment type, clinician perceptions, variables monitored and personalisation of alarm limits. Results: 65 participants completed the survey from 52 different NHS Trusts. 46% of Trusts had used telehealth for COPD, and currently, 31% still provided telehealth services to patients with COPD. Telehealth is most commonly used for baseline monitoring and to allow early detection of exacerbations, with 54% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate and breathlessness. A variety of methods were used to set alarm limits with the majority of respondents believing that at least 40% of alarms were false. Conclusion: Around one-third of responded community COPD services are using telehealth, believing it to be effective without robust evidence, with a variety of variables monitored, a variety of hardware and varying techniques to set alarm limits with high false alarm frequencies.