Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma.

BACKGROUND: Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin. METHODS: Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography-mass spectrometry. RESULTS: Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge. CONCLUSION: Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.

Urinary Leukotriene E4 as a Biomarker in NSAID-Exacerbated Respiratory Disease (N-ERD): a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Non-steroidal exacerbated respiratory disease (N-ERD) currently requires aspirin challenge testing for diagnosis. Urinary leukotriene E4 (uLTE4) has been extensively investigated as potential biomarker in N-ERD. We aimed to assess the usefulness of uLTE4 as a biomarker in the diagnosis of N-ERD. RECENT FINDINGS: N-ERD, formerly known as aspirin-intolerant asthma (AIA), is characterised by increased leukotriene production. uLTE4 indicates cysteinyl leukotriene production, and a potential biomarker in N-ERD. Although several studies and have examined the relationship between uLTE4 and N-ERD, the usefulness of uLTE4 as a biomarker in a clinical setting remains unclear. FINDINGS: Our literature search identified 38 unique eligible studies, 35 were included in the meta-analysis. Meta-analysis was performed (i.e. pooled standardised mean difference (SMD) with 95% confidence intervals (95% CI)) and risk of bias assessed (implementing Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy (Cochrane DTA)). Data from 3376 subjects was analysed (1354 N-ERD, 1420 ATA, and 602 HC). uLTE4 was higher in N-ERD vs ATA (n = 35, SMD 0.80; 95% CI 0.72-0.89). uLTE4 increased following aspirin challenge in N-ERD (n = 12, SMD 0.56; 95% CI 0.26-0.85) but not ATA (n = 8, SMD 0.12; CI - 0.08-0.33). This systematic review and meta-analysis showed that uLTE4 is higher in N-ERD than ATA or HC. Likewise, people with N-ERD have greater increases in uLTE4 following aspirin challenge. However, due to the varied uLTE4 measurement and result reporting practice, clinical utility of these findings is limited. Future studies should be standardised to increase clinical significance and interpretability of the results.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

BACKGROUND: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. METHODS: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. RESULTS: The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. CONCLUSION: Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Psychometric properties of patient reported outcome measures in idiopathic pulmonary fibrosis.

BACKGROUND: Various patient reported outcome measures (PROMs) are used in idiopathic pulmonary fibrosis (IPF). We aimed to describe their psychometric properties, assess their relationship with 1-year mortality and determine their minimal clinically important differences (MCIDs). METHODS: In a prospective multicentre study, participants with IPF completed the King's Brief Interstitial Lung Disease Questionnaire (K-BILD), the modified Medical Research Council (mMRC) dyspnoea scale, St George's Respiratory Questionnaire (SGRQ) and University of California, San Diego shortness of breath questionnaire (UCSD-SOBQ) three-monthly intervals over a 12-month period. Forced vital capacity (FVC) was matched with questionnaires and mortality was captured. Anchor- and distribution-based methods were used to derive MCID. RESULTS: Data were available from 238 participants. All PROMs had good internal consistency and high degree of correlations with other tools (except UCSD-SOBQ correlated poorly with FVC). There were significant associations with mortality for K-BILD (hazard ratio 16.67; 95% CI 2.38-100) and SGRQ (hazard ratio 4.65; 95% CI 1.32-16.62) but not with the other PROMs or FVC. The median MCID (range) for K-BILD was 6.3 (4.1-7.0), SGRQ was 7.0 (3.8-9.6), mMRC was 0.4 (0.1-0.5) and UCSD-SOBQ was 9.6 (4.1-14.2). CONCLUSIONS: The K-BILD was related to other severity measures and had the strongest relationship with mortality.

Developing and validating subjective and objective risk-assessment measures for predicting mortality after major surgery: An international prospective cohort study.

BACKGROUND: Preoperative risk prediction is important for guiding clinical decision-making and resource allocation. Clinicians frequently rely solely on their own clinical judgement for risk prediction rather than objective measures. We aimed to compare the accuracy of freely available objective surgical risk tools with subjective clinical assessment in predicting 30-day mortality. METHODS AND FINDINGS: We conducted a prospective observational study in 274 hospitals in the United Kingdom (UK), Australia, and New Zealand. For 1 week in 2017, prospective risk, surgical, and outcome data were collected on all adults aged 18 years and over undergoing surgery requiring at least a 1-night stay in hospital. Recruitment bias was avoided through an ethical waiver to patient consent; a mixture of rural, urban, district, and university hospitals participated. We compared subjective assessment with 3 previously published, open-access objective risk tools for predicting 30-day mortality: the Portsmouth-Physiology and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Surgical Risk Scale (SRS), and Surgical Outcome Risk Tool (SORT). We then developed a logistic regression model combining subjective assessment and the best objective tool and compared its performance to each constituent method alone. We included 22,631 patients in the study: 52.8% were female, median age was 62 years (interquartile range [IQR] 46 to 73 years), median postoperative length of stay was 3 days (IQR 1 to 6), and inpatient 30-day mortality was 1.4%. Clinicians used subjective assessment alone in 88.7% of cases. All methods overpredicted risk, but visual inspection of plots showed the SORT to have the best calibration. The SORT demonstrated the best discrimination of the objective tools (SORT Area Under Receiver Operating Characteristic curve [AUROC] = 0.90, 95% confidence interval [CI]: 0.88-0.92; P-POSSUM = 0.89, 95% CI 0.88-0.91; SRS = 0.85, 95% CI 0.82-0.87). Subjective assessment demonstrated good discrimination (AUROC = 0.89, 95% CI: 0.86-0.91) that was not different from the SORT (p = 0.309). Combining subjective assessment and the SORT improved discrimination (bootstrap optimism-corrected AUROC = 0.92, 95% CI: 0.90-0.94) and demonstrated continuous Net Reclassification Improvement (NRI = 0.13, 95% CI: 0.06-0.20, p < 0.001) compared with subjective assessment alone. Decision-curve analysis (DCA) confirmed the superiority of the SORT over other previously published models, and the SORT-clinical judgement model again performed best overall. Our study is limited by the low mortality rate, by the lack of blinding in the 'subjective' risk assessments, and because we only compared the performance of clinical risk scores as opposed to other prediction tools such as exercise testing or frailty assessment. CONCLUSIONS: In this study, we observed that the combination of subjective assessment with a parsimonious risk model improved perioperative risk estimation. This may be of value in helping clinicians allocate finite resources such as critical care and to support patient involvement in clinical decision-making.

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial.

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120.

Asthma, body mass and aerobic fitness, the relationship in adolescents: The exercise for asthma with commando Joe's® (X4ACJ) trial.

Although an association has been suggested between asthma, obesity, fitness and physical activity, the relationship between these parameters remains to be elucidated in adolescents. Six-hundred and sixteen adolescents were recruited (334 boys; 13.0 ± 1.1years; 1.57 ± 0.10m; 52.6 ± 12.9kg), of which 155 suffered from mild-to-moderate asthma (78 boys). Participants completed a 20-metre shuttle run test, lung function and 7-day objective physical activity measurements and completed asthma control and quality of life questionnaires. Furthermore, 69 adolescents (36 asthma; 21 boys) completed an incremental ramp cycle ergometer test. Although participants with asthma completed significantly fewer shuttle runs than their peers, peak V̇O2 did not differ between the groups. However, adolescents with asthma engaged in less physical activity (53.9 ± 23.5 vs 60.5 ± 23.6minutes) and had higher BMI (22.2 ± 4.8 vs 20.4 ± 3.7kg·m-2), than their peers. Whilst a significant relationship was found between quality of life and cardiorespiratory fitness according to peak V̇O2, only BMI was revealed as a significant predictor of asthma status. The current findings highlight the need to use accurate measures of cardiorespiratory fitness rather than indirect estimates to assess the influence of asthma during adolescence. Furthermore, the present study suggests that BMI and fitness may be key targets for future interventions seeking to improve asthma quality of life.

Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole). Objective: To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF. Design, Setting, and Participants: Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up). Interventions: Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily. Main Outcomes and Measures: The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores). Results: Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]). Conclusions and Relevance: Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo. Trial Registration: ISRCTN Identifier: ISRCTN17464641.

Elevated Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio Predicts Long-Term Mortality in High-Risk Patients.

BACKGROUND: Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio has been utilised as a predictor of outcomes in patients with adverse cardiometabolic risk profiles. In this study, we examined the prognostic value of elevated TG/HDL-C level in an Australian population of patients with high clinical suspicion of coronary artery disease (CAD) presenting for coronary angiography. METHODS: Follow-up data was collected for 482 patients who underwent coronary angiography in a prospective cohort study. The primary endpoint was all-cause mortality and the secondary endpoint was a major adverse cardiac event (MACE). Patients were stratified into two groups according to their baseline TG/HDL-C ratio, using a TG/HDL-C ratio cut point of 2.5. RESULTS: The mean follow-up period was 5.1 ± 1.2 years, with 49 all-cause deaths. Coronary artery disease on coronary angiography was more prevalent in patients with TG/HDL-C ratio ≥2.5 (83.6% vs. 69.4%, p = 0.03). On the Kaplan-Meier analysis, patients with TG/HDL-C ratio ≥2.5 had worse long-term prognosis (p = 0.04). On multivariate Cox regression adjusting for established cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was an independent predictor of long-term all-cause mortality (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.04-4.20, p = 0.04). On multivariate logistic regression adjusting for known cardiovascular risk factors and CAD on coronary angiography, TG/HDL-C ratio ≥2.5 was strongly associated with an increased risk of long-term MACE (odds ratio [OR] 2.72, 95% CI 1.42-5.20, p = 0.002). CONCLUSIONS: Elevated TG/HDL-C ratio is an independent predictor of long-term all-cause mortality and is strongly associated with an increased risk of MACE.

Breath biomarkers in idiopathic pulmonary fibrosis: a systematic review.

BACKGROUND: Exhaled biomarkers may be related to disease processes in idiopathic pulmonary fibrosis (IPF) however their clinical role remains unclear. We performed a systematic review to investigate whether breath biomarkers discriminate between patients with IPF and healthy controls. We also assessed correlation with lung function, ability to distinguish diagnostic subgroups and change in response to treatment. METHODS: MEDLINE, EMBASE and Web of Science databases were searched. Study selection was limited to adults with a diagnosis of IPF as per international guidelines. RESULTS: Of 1014 studies screened, fourteen fulfilled selection criteria and included 257 IPF patients. Twenty individual biomarkers discriminated between IPF and controls and four showed correlation with lung function. Meta-analysis of three studies indicated mean (± SD) alveolar nitric oxide (CalvNO) levels were significantly higher in IPF (8.5 ± 5.5 ppb) than controls (4.4 ± 2.2 ppb). Markers of oxidative stress in exhaled breath condensate, such as hydrogen peroxide and 8-isoprostane, were also discriminatory. Two breathomic studies have isolated discriminative compounds using mass spectrometry. There was a lack of studies assessing relevant treatment and none assessed differences in diagnostic subgroups. CONCLUSIONS: Evidence suggests CalvNO is higher in IPF, although studies were limited by small sample size. Further breathomic work may identify biomarkers with diagnostic and prognostic potential.

The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial.

AIMS: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalaemia to be associated with co-trimoxazole, which may stem from an amiloride-like potassium-sparing effect. The current study investigated changes in serum potassium in patients without acute infections, and the influence of concomitant antikaliuretic drugs on this effect. METHODS: A post hoc analysis was carried out of a randomized controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg co-trimoxazole twice daily. Serum potassium and creatinine were measured at baseline, 6 weeks, and 6, 9 and 12 months. The primary outcome was the difference in mean serum potassium concentrations between co-trimoxazole and placebo at 6 weeks. RESULTS: Mean serum potassium levels were similar at baseline: 4.24 (± 0.44) mmol l-1 in the 87 co-trimoxazole group participants and 4.25 (± 0.39) mmol l-1 in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium levels at 6 weeks, with a difference between means compared with placebo of 0.21 mmol l-1 [95% confidence interval (CI) 0.09, 0.34; P = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on antikaliuretic drugs, with a difference between means for co-trimoxazole compared with placebo of 0.23 mmol l-1 (95% CI 0.09, 0.38; P = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium concentrations reached ≥5.5 mmol l-1 during the study period. CONCLUSIONS: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.

Managing fatigue in sarcoidosis - A systematic review of the evidence.

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended.

The Index of Microcirculatory Resistance Postpercutaneous Coronary Intervention Predicts Left Ventricular Recovery in Patients With Thrombolyzed ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The index of microcirculatory resistance (IMR), an invasive measure of microvascular function, has been shown to correlate with clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study is to evaluate the predictive value of IMR on left ventricular recovery in patients undergoing a pharmacoinvasive strategy for STEMI. METHODS: The index of microcirculatory resistance was assessed following percutaneous coronary intervention (PCI) in 31 patients with STEMI who were initially managed with thrombolysis. Other markers of microvascular function such as coronary flow reserve (CFR), TIMI flow grade, corrected TIMI frame count (cTFC), and ST-segment resolution were also recorded. All indices were evaluated against measures of left ventricular function and recovery 3 months postindex event. RESULTS: The IMR correlated with left ventricular function, as assessed by wall motion score and ejection fraction at 3-month follow-up (r = 0.652, P = 0.005; r = -0.452, P = 0.011, respectively). The traditional methods of assessing microvascular function, such as CFR, TIMI flow grade, cTFC, and ST-segment resolution did not correlate with wall motion score and ejection fraction at 3 months. Post-PCI IMR was significantly lower in those patients with left ventricular recovery at 3 months (18 U vs 39 U, P < 0.001). The optimal cut-off value for post-PCI IMR and left ventricular recovery was 32 U. In patients in whom the IMR was greater than 32 U, the percent change in ejection fraction was significantly lower than in those patients in whom the IMR was less than 32 U (2 ± 11 vs 12 ± 8, P = 0.012). CONCLUSIONS: In patients presenting with STEMI initially managed with thrombolysis and subsequently undergoing PCI, IMR correlates with measures of left ventricular function and has the potential to predict left ventricular recovery at 3 months.

Two Cases of Right Atrial Mural Endocarditis Caused by Staphylococcus Aureus.

Mural endocarditis is a rare clinical entity with an extremely high mortality rate. It is usually predisposed by an underlying structural intracardiac abnormality. We present two cases of mural endocarditis occurring in the right atrium which were complicated by septic pulmonary embolism, one of which was predisposed by a jet lesion secondary to a coronary artery fistula. Both cases were successfully managed conservatively with excellent long-term outcomes.

Airways resistance in bronchial challenge testing.

INTRODUCTION: Measurement of airways resistance is an alternative to spirometry to assess airflow obstruction. This can be measured by the interrupter technique (RInt) using a handheld device. We wished to know how RInt compared to forced expiratory volume in 1 s (FEV1) during a histamine challenge test. METHODS: Twenty-nine (13 male) patients, aged 48.9 (SD 15.3) years, referred for a histamine challenge test, were enrolled. Patients had measurement of RInt then FEV1 after administration of saline and following doubling concentrations of histamine from 0.06 to 8 mg/ml. Extrapolation of the log dose-response curve was undertaken to calculate the concentration (provocation concentration, PC) causing an increase airways resistance of 20, 40, 60, 80, 100, 120, 140 and 160% (RInt PC1.2 to RInt PC2.6) and a reduction in FEV1 by 20% (FEV1 PC20). The number of patients with a negative challenge (i.e. PC>8 mg/ml histamine) was calculated for FEV1 and each change in airway resistance. Patients assessed their procedure-provoked symptoms of breathlessness, dizziness and tiredness on a visual analogue scale. RESULTS: Geometric (SD) PC20 for FEV1 was 1.87 (0.5) mg/ml with 11 patients having a negative challenge. A RInt PC20 had the best agreement with FEV1 PC20 [Kappa 0.39 (p=0.024)]. There is a significant negative correlation between RInt and FEV1 (r=-0.94). The respective mean (SD) breathlessness, dizziness and tiredness scores for RInt were 26 (4) mm, 18 (3) mm, 22 (4) mm and for spirometry were 40 (4) mm, 27 (5) mm, 31 (5) mm. There was a significant (p<0.05) difference for breathlessness. CONCLUSION: RInt was tolerated better than spirometry. A doubling of airways resistance had the best agreement with PC20 FEV1.

Managing chronic rhinosinusitis and respiratory disease: a qualitative study of triggers and interactions.

OBJECTIVE: The aim of this analysis is to explore views of patients with chronic rhinosinusitis (CRS) about of the aetiology of their respiratory symptoms and the relationship between upper and lower respiratory symptoms. METHODS: This study is part of a larger mixed methods study investigating the epidemiology of CRS, which comprises a questionnaire study of patients with CRS and controls and a qualitative study of 21 patients with CRS. Semi structured qualitative interviews were undertaken with these patients; 11 males and 10 females. Twelve patients had asthma. Patients were recruited with a tertiary outpatient rhinology clinic. Interviews were transcribed verbatim and analysed using thematic analysis, using Nvivo software (QSR International, Melbourne, Australia). Several important and recurring themes were highlighted. RESULTS: Patients described many perceived triggering factors and an interaction between upper and lower respiratory tract symptoms. They felt that their symptoms could be managed more holistically. CONCLUSIONS: Concerns about triggers of respiratory symptoms and interactions between upper and lower respiratory symptoms are of significant concern to patients. These should be appropriately managed and acknowledged in formal treatment pathways, for example, through the use of combined ENT/respiratory clinics.

A twist in the transradial coronary catheterisation.

The transradial approach for coronary angiography was first described in 1989. With the advent of modern equipment and improved technology it has recently gained significant interest amongst interventional cardiologists. As compared to femoral access, the radial approach has the major advantages of lower access site complication rates, cost-effectiveness, and shorter hospital stays. Further clinical benefits of lower morbidity and cardiac mortality in patients with ST-elevation myocardial infarction have been shown recently. Rare vascular complications may include radial artery spasm, dissection, occlusion, perforation or compartment syndrome. Here, we present two unusual cases of an entrapped catheter in the radial artery and their outcomes.

Assessment of the impact of social deprivation, distance to hospital and time to diagnosis on survival in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive condition associated with a variable prognosis. The relationship between socioeconomic status or distance travelled to respiratory clinics and prognosis is unclear. RESEARCH QUESTION: To determine whether socioeconomic status, distance to hospital and time to referral affects survival in patients with IPF. STUDY DESIGN AND METHODS: In this retrospective cohort study, we used data collected from the British Thoracic Society Interstitial Lung Diseases Registry, between 2013 and 2021 (n = 2359) and calculated the quintile of Index of Multiple Deprivation 2019 score, time from initial symptoms to hospital attendance and distance as the linear distance between hospital and home post codes. Survival was assessed using Cox proportional hazards models. RESULTS: There was a significant association between increasing quintile of deprivation and duration of symptoms prior to hospital presentation, Gender Age Physiology (GAP) index and receipt of supplemental oxygen and antifibrotic therapies at presentation. The most deprived patients had worse overall survival compared to least deprived after adjusting for smoking status, GAP index, distance to hospital and time to referral (HR = 1.39 [1.11, 1.73]; p = 0.003). Patients living furthest from a respiratory clinic also had worse survival compared to those living closest (HR = 1.29 [1.01, 1.64]; p = 0.041). INTERPRETATION: The most deprived patients with IPF have more severe disease at presentation and worse outcomes. Living far from hospital was also associated with poor outcomes. This suggests inequalities in access to healthcare and requires consideration in delivering effective and equitable care to patients with IPF.