Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study.

BACKGROUND: Over 30% of adult patients with pleural infection either die and/or require surgery. There is no robust means of predicting at baseline presentation which patients will suffer a poor clinical outcome. A validated risk prediction score would allow early identification of high-risk patients, potentially directing more aggressive treatment thereafter. OBJECTIVES: To prospectively assess a previously described risk score (the RAPID (Renal (urea), Age, fluid Purulence, Infection source, Dietary (albumin)) score) in adults with pleural infection. METHODS: Prospective observational cohort study that recruited patients undergoing treatment for pleural infection. RAPID score and risk category were calculated at baseline presentation. The primary outcome was mortality at 3 months; secondary outcomes were mortality at 12 months, length of hospital stay, need for thoracic surgery, failure of medical treatment and lung function at 3 months. RESULTS: Mortality data were available in 542 out of 546 patients recruited (99.3%). Overall mortality was 10% at 3 months (54 out of 542) and 19% at 12 months (102 out of 542). The RAPID risk category predicted mortality at 3 months. Low-risk mortality (RAPID score 0-2): five out of 222 (2.3%, 95% CI 0.9 to 5.7%); medium-risk mortality (RAPID score 3-4): 21 out of 228 (9.2%, 95% CI 6.0 to 13.7%); and high-risk mortality (RAPID score 5-7): 27 out of 92 (29.3%, 95% CI 21.0 to 39.2%). C-statistics for the scores at 3 months and 12 months were 0.78 (95% CI 0.71-0.83) and 0.77 (95% CI 0.72-0.82), respectively. CONCLUSIONS: The RAPID score stratifies adults with pleural infection according to increasing risk of mortality and should inform future research directed at improving outcomes in this patient population.

A quality assessment of respiratory auscultation material on YouTube.

YouTube contains a large volume of medical educational material. This study assessed the quality of respiratory auscultation videos contained in YouTube. Videos were searched for using the terms 'breath sounds', 'respiratory sounds', 'respiratory auscultation' and/or 'lung sounds'. In total, 6,022 videos were located, 36 of which were considered suitable for scoring for video accuracy, comprehensiveness and quality. The average score was 3.32/6 (55.3% ± 1.30). Video score correlated with time-adjusted YouTube metadata: hits per day (0.496, p=0.002) and likes per day (0.534, p=0.001). Video score also correlated with the first search page on which the video was located in the 'breath sounds' and 'lung sounds' searches (-0.571, p=0.001; -0.445, p=0.014, respectively). The quality of videos was variable. Correlation between video score and some metadata values suggests that there is value for their use in judging video quality. However, the large number of videos found and inability to filter these results quickly makes locating educational content difficult.

Non-invasive biomarkers in exacerbations of obstructive lung disease.

BACKGROUND AND OBJECTIVE: Current methods of diagnosing exacerbations of asthma and chronic obstructive pulmonary disease (COPD) shed little light on their aetiology or pathophysiology. This study aimed to define the inflammatory biomarker profile of subjects with obstructive lung disease and to compare these with control subjects also with respiratory infections, using exhaled breath condensate (EBC) and induced sputum biomarker analysis. METHODS: EBC, induced sputum and C-reactive protein were collected from subjects with exacerbations of asthma (n = 28), exacerbations of COPD (n = 29) and otherwise healthy controls with symptoms of respiratory tract infection (n = 28). Subjects were tested again after recovery. EBC and induced sputum were analysed for protein, hydrogen peroxide, interferon gamma inducible protein-10 (IP-10), neopterin, interleukin (IL)-6, IL-8, leukotriene B4 and tumour necrosis factor (TNF)-α. Sputum cell counts and EBC pH were also analysed. RESULTS: EBC pH was significantly lower in exacerbation compared with recovery (5.54 0.07 vs 6.04 ± 0.08; P < 0.001). The novel markers IP-10 and neopterin were significantly increased in induced sputum supernatant (pooled groups pre and post exacerbation: IP-10: 188.6 ± 102.1 vs 5.40 ± 1.28 pg/mL, P = 0.006; neopterin: 15.81 ± 2.50 vs 5.38 ± 0.45 nmol/L, P < 0.0001), as was TNF-α (137.8 ± 49.64 vs 71.56 ± 45.03 pg/mL, P = 0.018). Few other biomarkers proved significantly different in exacerbation, although C-reactive protein was raised. CONCLUSIONS: Non-invasive biomarker assessment may provide useful information in exacerbation of obstructive lung diseases, particularly sputum IP-10 and neopterin and EBC pH.

Improving outcomes in patients with cystic fibrosis.

Cystic fibrosis (CF) is the most common fatal inherited disease in Caucasian people. Inheritance follows an autosomal recessive pattern. Recent data indicate that there are more than 9,000 patients with CF in the UK. At a cellular level there is an abnormal CF transmembrane conductance regulator (CFTR), a protein essential for chloride and sodium homoeostasis, caused by a mutation in the CF gene. The consequence of this abnormal protein is thick, viscous secretions in the lungs and GI tract, which lead to recurrent lung infections and pancreatic insufficiency with intestinal malabsorption. Most patients present in early childhood with classic CF. They show one or more of the typical CF phenotypic characteristics (chronic pulmonary disease, GI symptoms and malabsorption, nutritional abnormalities and sinus disease). A minority of patients have atypical CF. They tend to present at an older age, often in adulthood, are mainly pancreatic sufficient, have milder disease and a better prognosis. When CF is suspected the diagnosis can be confirmed by measuring sweat chloride concentration and by looking for CFTR mutations. Immunoreactive trypsinogen is measured in blood taken from a heel prick in all neonates, and is a marker of pancreatic injury consistent with (but not specific for) CF.

Chest radiography is a poor predictor of respiratory symptoms and functional impairment in survivors of severe COVID-19 pneumonia.

BACKGROUND: A standardised approach to assessing COVID-19 survivors has not been established, largely due to the paucity of data on medium- and long-term sequelae. Interval chest radiography is recommended following community-acquired pneumonia; however, its utility in monitoring recovery from COVID-19 pneumonia remains unclear. METHODS: This was a prospective single-centre observational cohort study. Patients hospitalised with severe COVID-19 pneumonia (admission duration ≥48 h and oxygen requirement ≥40% or critical care admission) underwent face-to-face assessment at 4-6 weeks post-discharge. The primary outcome was radiological resolution of COVID-19 pneumonitis (Radiographic Assessment of Lung Oedema score <5). Secondary outcomes included clinical outcomes, symptom questionnaires, mental health screening (Trauma Screening Questionnaire, seven-item Generalised Anxiety Disorder assessment and nine-item Patient Health Questionnaire) and physiological testing (4-m gait speed (4MGS) and 1-min Sit-to-Stand (STS) tests). RESULTS: 119 patients were assessed between June 3, 2020 and July 2, 2020 at median (interquartile range (IQR)) 61 (51-67) days post-discharge: mean±sd age 58.7±14.4 years, median (IQR) body mass index 30.0 (25.9-35.2) kg·m-2, 62% male and 70% ethnic minority. Despite radiographic resolution of pulmonary infiltrates in 87%, modified Medical Research Council Dyspnoea (breathlessness) scale grades were above pre-COVID-19 baseline in 44%, and patients reported persistent fatigue (68%), sleep disturbance (57%) and breathlessness (32%). Screening thresholds were breached for post-traumatic stress disorder (25%), anxiety (22%) and depression (18%). 4MGS was slow (<0.8 m·s-1) in 38% and 35% desaturated by ≥4% during the STS test. Of 56 thoracic computed tomography scans performed, 75% demonstrated COVID-19-related interstitial and/or airways disease. CONCLUSIONS: Persistent symptoms, adverse mental health outcomes and physiological impairment are common 2 months after severe COVID-19 pneumonia. Follow-up chest radiography is a poor marker of recovery; therefore, holistic face-to-face assessment is recommended to facilitate early recognition and management of post-COVID-19 sequelae.

Breathlessness and dysfunctional breathing in patients with postural orthostatic tachycardia syndrome (POTS): The impact of a physiotherapy intervention.

Postural orthostatic tachycardia syndrome (POTS) is a chronic, multifactorial syndrome with complex symptoms of orthostatic intolerance. Breathlessness is a prevalent symptom, however little is known about the aetiology. Anecdotal evidence suggests that breathless POTS patients commonly demonstrate dysfunctional breathing/hyperventilation syndrome (DB/HVS). There are, however, no published data regarding DB/HVS in POTS, and whether physiotherapy/breathing retraining may improve patients' breathing pattern and symptoms. The aim of this study was to explore the potential impact of a physiotherapy intervention involving education and breathing control on DB/HVS in POTS. A retrospective observational cohort study of all patients with POTS referred to respiratory physiotherapy for treatment of DB/HVS over a 20-month period was undertaken. 100 patients (99 female, mean (standard deviation) age 31 (12) years) with a clinical diagnosis of DB/HV were referred, of which data was available for 66 patients pre - post intervention. Significant improvements in Nijmegen score, respiratory rate and breath hold time (seconds) were observed following treatment. These data provide a testable hypothesis that breathing retraining may provide breathless POTS patients with some symptomatic relief, thus improving their health-related quality of life. The intervention can be easily protocolised to ensure treatment fidelity. Our preliminary findings provide a platform for a subsequent randomised controlled trial of breathing retraining in POTS.

Developing an integrated rehabilitation model for thoracic cancer services: views of patients, informal carers and clinicians.

BACKGROUND: Access to rehabilitation to prevent disability and optimise function is recommended for patients with cancer, including following cancer diagnosis. Models to integrate rehabilitation within oncology services as cancer treatment commences are required, but must be informed by those they are intended to support. We aimed to identify views of patients, carers and clinicians to develop and refine a rehabilitation model to be tested in a feasibility trial for people newly diagnosed with lung cancer or mesothelioma. METHODS: We conducted a focus group study with people affected by lung cancer or mesothelioma, their carers and clinicians providing their care to identify priorities for rehabilitation in this period. We sought views on core intervention components, processes and outcomes and integration with oncology services. Data were analysed using thematic analysis. RESULTS: Fifteen clinicians (oncologists, nurse specialists, physiotherapists and occupational therapists), nine patients and five carers participated. A proposed outline rehabilitation model was perceived as highly relevant for this population. Participants recommended prompt and brief rehabilitation input, delivered whilst people attend for hospital appointments or at home to maximise accessibility and acceptability. Participants recognised variation in need and all prioritised tailored support for symptom self-management, daily activities and the involvement of carers. Clinicians also prioritised achieving fitness for oncology treatment. Patients and carers prioritised a sensitive manner of approach, positivity and giving hope for the future. Participant's recommendations for outcome measurement related to confidence in usual daily activities, symptom control and oncology treatment completion rates over objective measures of cardiorespiratory fitness. CONCLUSION: The importance of providing tailored rehabilitation around the time of diagnosis for people with lung cancer or mesothelioma was affirmed by all participants. The refined model of rehabilitation recommended for testing in a feasibility trial is flexible, tailored and short-term. It aims to support people to self-manage symptoms, tolerate cancer treatments and to remain active and independent in daily life. It is delivered alongside scheduled hospital appointments or at home by an expert practitioner sensitive to the psycho-social sequelae that follow a diagnosis of thoracic cancer.

Exhaled breath condensate in pulmonary arterial hypertension.

Over the last decade, several new agents have been developed for the treatment of pulmonary arterial hypertension (PAH), and blood biomarkers have been developed which aim to monitor such treatment, and which correlate well with physiological parameters, symptoms and mortality. However, little is known regarding biomarkers collected using non-invasive methods such as exhaled breath condensate (EBC). EBC biomarkers show potential as a rapid, repeatable and easy method of sampling the pulmonary vasculature in severely ill patients. The current study aimed to investigate EBC biomarkers in patients with PAH of different aetiologies. We studied 89 patients in four groups: pulmonary arterial hypertension (PAH, n = 30), PAH associated with COPD (COPD/PAH, n = 14), COPD but no PAH (n = 16) and healthy controls (n = 29). Levels of the following EBC markers were measured: amino-terminal pro-brain natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), 6-keto prostaglandin (PG)F(1α), hydrogen peroxide (H(2)O(2)), total oxides of nitrogen (NO(x)), total protein and pH. ET-1 and NT-proBNP were measured in plasma concurrently. Data were analysed with ANOVA or Kruskal Wallis tests where appropriate. Correlations were performed using Pearson's correlation coefficient. NT-proBNP was detectable in EBC and was highest in the PAH group, significantly higher than the COPD/PAH group (194.1 ± 23.3 versus 80.8 ± 22.2 fmol ml(-1), p < 0.05). EBC ET-1 was significantly higher in subjects with PAH (1.53 ± 0.32 fmol ml(-1)) compared to those with COPD/PAH (0.25 ± 0.03 fmol ml(-1), p < 0.05) and controls (0.66 ± 0.18 fmol ml(-1), p < 0.05). 6-keto PGF(1α) was low in the PAH group, significantly lower than the COPD/PAH group (4027 ± 445 versus 8381 ± 1024 pg ml(-1), p < 0.01). EBC biomarkers are measurable in PAH. EBC ET-1 was raised in PAH compared with controls and patients with PAH secondary to COPD, whereas 6-keto PGF(1α) was low. EBC biomarkers may be useful in detection and monitoring of PAH.

The effect of temperature on exhaled breath condensate collection.

Exhaled breath condensate (EBC) collection is an innovative method of non-invasively sampling the lung, and can detect a variety of volatile and non-volatile biomarkers, but the disadvantage is the small volume of sample collected. It was hypothesized that a collection system at a lower temperature would increase the volume collected, but may alter the relative concentration of the biomarkers of interest. EBC was collected in a cross-over study using a custom-made collection system, cooled using either wet (4 °C) or dry ice (-20 °C) in randomized order in normal non-smoking volunteers. The volume of the EBC collected per unit time was determined as were conductivity, the concentrations and total amount of protein, hydrogen peroxide, and nitrite/nitrate concentrations. Dry ice was associated with a 79% greater volume of EBC than the wet ice (1387 ± 612 µL; 773 ± 448 µL respectively, p < 0.0001). Conductivity was influenced by the temperature of collection (18.78 ± 6.71 µS cm(-1) for wet ice and 15.32 ± 6.28 µS cm(-1) for dry ice, p = 0.02) as was hydrogen peroxide (1.34 ± 0.88 µg mL(-1) for wet ice and 0.68 ± 0.32 µg mL(-1) for dry ice, p = 0.009) while the concentrations and total values for protein and nitrate/nitrite were not significantly different (p > 0.05). This pilot study suggests that lower collection temperatures facilitate the collection of a larger sample volume. This larger volume is not simply more dilute, with increased water content, nor is there a simple correction factor that can be applied to the EBC biomarkers to correct for the different methods.

Renal cancer associated with recurrent spontaneous pneumothorax in Birt-Hogg-Dubé syndrome: a case report and review of the literature.

INTRODUCTION: Birt-Hogg-Dubé syndrome is a rare genodermatosis characterized by hair follicle hamartomas, renal tumors and spontaneous pneumothorax. We present the case of a patient with pulmonary cysts and recurrent spontaneous pneumothorax. She had typical skin lesions, and was found to have a hybrid oncocytoma which was surgically excised. CASE PRESENTATION: A 60-year-old Caucasian woman had a 10-year history of cystic lung disease and recurrent spontaneous pneumothoraces. She was noted to have papular lesions over her face and forehead. The result of a biopsy showed these lesions to be fibrofolliculomas. A diagnosis of Birt-Hogg-Dubé syndrome was made and she was screened for renal tumors since these are a recognized association. A hybrid oncocytoma was detected which was surgically excised by partial nephrectomy. CONCLUSION: It is important to consider a possible diagnosis of Birt-Hogg-Dubé syndrome in cases of recurrent pneumothorax. Affected individuals must be screened for renal tumors, a potentially lethal consequence of this syndrome.