Quantification of smooth muscle in human airways by polarization-sensitive optical coherence tomography requires correction for perichondrium.

Quantifying airway smooth muscle (ASM) in patients with asthma raises the possibility of improved and personalized disease management. Endobronchial polarization-sensitive optical coherence tomography (PS-OCT) is a promising quantitative imaging approach that is in the early stages of clinical translation. To date, only animal tissues have been used to assess the accuracy of PS-OCT to quantify absolute (rather than relative) ASM in cross sections with directly matched histological cross sections as validation. We report the use of whole fresh human and pig airways to perform a detailed side-by-side qualitative and quantitative validation of PS-OCT against gold-standard histology. We matched and quantified 120 sections from five human and seven pig (small and large) airways and linked PS-OCT signatures of ASM to the tissue structural appearance in histology. Notably, we found that human cartilage perichondrium can share with ASM the properties of birefringence and circumferential alignment of fibers, making it a significant confounder for ASM detection. Measurements not corrected for perichondrium overestimated ASM content several-fold (P < 0.001, paired t test). After careful exclusion of perichondrium, we found a strong positive correlation (r = 0.96, P < 0.00001) of ASM area measured by PS-OCT and histology, supporting the method's application in human subjects. Matching human histology further indicated that PS-OCT allows conclusions on the intralayer composition and in turn potential contractile capacity of ASM bands. Together these results form a reliable basis for future clinical studies.NEW & NOTEWORTHY Polarization-sensitive optical coherence tomography (PS-OCT) may facilitate in vivo measurement of airway smooth muscle (ASM). We present a quantitative validation correlating absolute ASM area from PS-OCT to directly matched histological cross sections using human tissue. A major confounder for ASM quantification was observed and resolved: fibrous perichondrium surrounding hyaline cartilage in human airways presents a PS-OCT signature similar to ASM for birefringence and optic axis orientation. Findings impact the development of automated methods for ASM segmentation.

Who Am I? Self-concept in Adults with Cystic Fibrosis: Association with Anxiety and Depression.

Cystic Fibrosis (CF) is a progressive condition resulting in reduced lung function and strongly associated with elevated anxiety and depression symptoms. Self-concept refers to an individual's overarching sense of identity, a positive level of which is widely associated with reduced anxiety and depression. There is a significant lack of self-concept research within CF. This study explores the association between self-concept and anxiety and depression in adults with CF. 64 adults living with CF in Western Australia completed validated online questionnaires (Generalised Anxiety Disorder-7, Patient Health Questionnaire-9, Tennessee Self-Concept Questionnaire 2: Short-Form) and consented to the collection of medical data. Descriptive, t-test, correlation and multiple regression analysis were undertaken. Higher levels of self-concept were associated with lower levels of anxiety and depression symptoms. Lower self-concept levels were a significant predictor of increased anxiety and depression symptoms after accounting for physical health status. Mean self-concept scores for those who required mental health intervention were significantly lower compared to those that did not. This study identifies a significant relationship between self-concept and anxiety and depression in adults with CF. Further research is required to establish causation and test the feasibility of self-concept interventions in reducing anxiety and depression symptoms.

Beyond the Lungs-Emerging Challenges in Adult Cystic Fibrosis Care.

Cystic fibrosis (CF) is a multisystem disease. This article provides an up-to-date review of many of the nonrespiratory complications of CF, including mental health issues, nutritional and gastrointestinal problems, fertility issues, diabetes mellitus, bone health and musculoskeletal problems, liver disease, renal problems, and risk of malignancy. It highlights the recent impact of new therapies, including CF transmembrane conductance regulator modulators, on the nonrespiratory complications of CF and provides insights into the potential challenges faced by an aging population of adults with CF and their caregivers, including the potential future risk for cardiovascular disease.

U-shaped association of vigorous physical activity with risk of metabolic syndrome in men with low lean mass, and no interaction of physical activity and serum 25-hydroxyvitamin D with metabolic syndrome risk.

BACKGROUND: There is uncertainty over how lean mass, physical activity (PA) and 25-hydroxyvitamin D (25-OH-D) status interact on metabolic syndrome (MetS) risk in adults. AIMS: To test the hypothesis that these factors additively influence MetS risk. METHODS: Four thousand eight hundred and fifty-eight adults (54.6% female) mean ± SD age 58.0 ± 5.8 years, body mass index 28.1 ± 4.8 kg/m2 , resident in Busselton, Western Australia. PA assessed by questionnaire (all/total and vigorous), lean mass using dual energy X-ray absorptiometry (% total body mass), serum 25-OH-D via immunoassay, analysed using multivariable logistic regression. RESULTS: In men, lower total PA was associated with MetS (no vs >24 h/week odds ratio (OR) = 3.1; ≤8 vs >24 h/week OR = 1.8, both P < 0.001), as was lower lean mass (low vs high OR = 20.4; medium vs high OR = 7.4, both P < 0.001). Men with low lean mass exhibited a U-shaped relationship of vigorous PA with MetS risk (covariate-adjusted: 0 vs 4-8 h/week OR = 2.1, P = 0.037; >12 vs 4-8 h/week OR = 4.3, P = 0.002; interaction P = 0.039). In women, low PA (0 vs >24 h/week OR = 2.1, P = 0.003) and lean mass (low vs high OR = 13.1; medium vs high OR = 7.2, both P < 0.001) were associated with MetS risk. Low 25-OH-D status was associated with MetS in men (low vs high OR = 4.1; medium vs high OR = 2.3, both P < 0.001) and women (OR = 3.5 and 2.1 respectively, both P < 0.001) with no PA interaction. CONCLUSIONS: Men and women with high lean mass have low risk of MetS regardless of PA. Low lean mass identifies men who may benefit most from increasing PA, with an optimal level associated with lowest risk. 25-OH-D and PA do not interact on MetS risk.

Tracheobronchitis in ulcerative colitis: a case report of therapeutic response with infliximab and review of the literature.

BACKGROUND: The extra-intestinal manifestation of tracheobronchitis is a rare complication of ulcerative colitis (UC). Here, we present a case of UC-related tracheobronchitis wherein the positive clinical effects of infliximab are demonstrated. CASE PRESENTATION: We report the case of a 39-year old woman who presented with a chronic productive cough on a distant background of surgically managed ulcerative colitis (UC). Our patient failed to achieve a satisfactory clinical improvement despite treatment with high dose inhaled corticosteroids, oral corticosteroids and azathioprine. Infliximab therapy was commenced and was demonstrated to achieve macroscopic and symptomatic remission of disease. CONCLUSIONS: We present the first case report documenting the benefits of infliximab in UC-related tracheobronchitis.

The significance of anti-granulocyte-macrophage colony-stimulating factor antibodies in cryptococcal infection: case series and review of antibody testing.

We report two cases of cryptococcosis, associated with anti-granulocyte-macrophage colony-stimulating factor antibodies. We review this recently identified acquired form of autoimmune immune deficiency and discuss the potential applications of granulocyte-macrophage colony-stimulating factor antibody testing by enzyme-linked immunosorbent assay.

A pragmatic application of endobronchial ultrasound-guided transbronchial needle aspiration: a single institution experience.

BACKGROUND: Endobronchial ultrasound-guided trans-bronchial needle aspiration (EBUS-TBNA) is minimally invasive technique used for diagnosis and/or staging of benign and malignant pulmonary and non-pulmonary disease. Previous studies have established the utility of EBUS-TBNA in narrowly defined indications and populations. In this pragmatic 'real world' study we have analysed the use of EBUS-TBNA for a variety of clinical presentations and its clinical application in conjunction with other invasive investigations. METHODS: All EBUS-TBNA procedures performed at Sir Charles Gardiner Hospital in 2012-2014 were reviewed retrospectively, using relevant hospital databases. RESULTS: A total of 327 patients underwent 337 EBUS-TBNA procedures. EBUS-TBNA procedures were used to diagnose a wide spectrum of benign and malignant conditions. The main application was in the diagnosis and staging of malignant conditions (70.6%), and in the diagnosis of benign conditions such as sarcoidosis 40 (12.2%), and silicoanthracosis 17 (5.2%). EBUS-TBNA was sufficient to diagnose and stage the disease as a single stand-alone invasive procedure in 191 (59.2%) patients. EBUS-TBNA was the final invasive procedure undertaken in 283 (87.6%) patients. Only 13.3% of non small cell lung cancer (NSCLC) patients who had EBUS-TBNA as a first investigation required multiple procedures compared to 51.1% of all NSCLC patients undergoing EBUS-TBNA. Overall sensitivity, specificity, NPV and diagnostic accuracy for EBUS-TBNA were 89.7, 100, 85.1 and 89.9%, respectively and three minor complications (0.9%) occurred as a result of the procedure. CONCLUSIONS: EBUS-TBNA was undertaken for a wide variety of clinical conditions. Good diagnostic accuracy and safety profiles were demonstrated for the procedure, supporting its application as a first line investigation in the diagnosis and/or staging of a range of malignant and benign conditions. Our study was unique in its documentation of the use of EBUS-TBNA in a real-world setting in conjunction with other invasive modalities. EBUS-TBNA was utilised as a stand alone invasive procedure in more than half of the patients. Importantly, in NSCLC, when EBUS-TBNA was performed as primary diagnostic and staging investigation, less patients underwent subsequent invasive procedures.

Vitamin D and respiratory health in the Busselton Healthy Ageing Study.

BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). CONCLUSION: Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.

Estimating eligibility for lung cancer screening in an Australian cohort, including the effect of spirometry.

OBJECTIVES: To estimate the proportion of ever-smokers who are eligible for lung cancer screening in an Australian cohort, and to evaluate the effect of spirometry in defining chronic obstructive pulmonary disease (COPD) when assessing screening eligibility. DESIGN: Cross-sectional study of 3586 individuals aged 50-68 years who live in the Busselton Shire of Western Australia. OUTCOMES: Proportion of ever-smokers eligible for lung cancer screening based on United States Preventive Services Task Force (USPSTF) criteria, and PLCOm2012 lung cancer risk > 1.5%. The effect of using self-reported COPD, symptoms consistent with COPD, or spirometry to define COPD for screening eligibility according to the PLCOm2012 criteria. RESULTS: Of ever-smokers aged 55-68 years, 254 (20.1%) would be eligible for screening according to USPSTF criteria; fewer would be eligible according to PLCOm2012 criteria (225, 17.9%; P = 0.004). This is equivalent to 8.9-10.0% of the total population aged 55-68 years, which suggests about 450 000 individuals in Australia may be eligible for lung cancer screening. The proportions of eligible participants were not significantly different whether spirometry results or symptoms consistent with COPD were used to determine PLCOm2012 risk. CONCLUSIONS: The proportion of ever-smokers in this population who were eligible for lung cancer screening was 17.9-20.1%. Using symptoms to define COPD is an appropriate surrogate measure for spirometry when determining the presence of COPD in this population. There are significant challenges for policy makers on how to identify and recruit these eligible individuals from the wider population.

Recommencement of atezolizumab with associated pulmonary sarcoid-like reaction.

An 81 year old male with Child-Pugh A cirrhosis and metastatic hepatocellular carcinoma (HCC) treated with 3-weekly atezolizumab and bevacizumab developed a pulmonary sarcoid-like reaction (SLR) after 5 months. Atezolizumab, an immune checkpoint inhibitor, was identified as the likely culprit. He was treated with prednisolone, resulting in improvement, and was successfully rechallenged with both atezolizumab and bevacizumab.

Me, myself, and I: A systematic review of cystic fibrosis and self-concept.

Given extensive pertinent disease factors and evolving medical treatments, this systematic review explores qualitative and quantitative cystic fibrosis (CF) research surrounding self-concept, an overarching perception of self. Research methodologies, self-concept dimensions, prominent self-concept findings and clinical recommendations are identified. Preferred Reporting Items for Systematic Review and Meta-analyses guidelines were applied. PubMed, Scopus, Medline, Psycinfo, CINAHL (ebsco), and CENTRAL Cochrane electronic databases were searched from 2012 to 2022. Methodological quality was assessed using the critical appraisal skills program. Data-based convergent synthesis was applied to analyze and report on qualitative and quantitative studies in parallel. Thirty-seven publications met the inclusion criteria, most of which employed a cross-sectional, single-center design within an adolescent and adult population. Self-efficacy, self-esteem, and self-identity studies were dimensions of self-concept identified, with studies relating to self-efficacy surrounding physical health management most prevalent. All three dimensions were positively associated with improved treatment adherence and psychosocial health. Efficacy tested intervention programs to enhance self-concept are limited; however, an extensive range of clinical recommendations are offered, highlighting the importance of clinician self-concept awareness, quality clinician-patient conversations and online CF peer-support. Self-concept is an important mechanism to optimize patient outcomes. Further CF self-concept research is required, particularly multicenter, longitudinal, and interventional studies. Early childhood, post lung transplant and the older adult CF population in particular, lack research attention. Given the potential impact of rapidly evolving CF transmembrane conductance regulator modulator drugs on many aspects of self, future self-concept research beyond the dimension of self-efficacy may be beneficial.

Risk factors for respiratory symptoms in adults: the Busselton Health Study.

BACKGROUND AND OBJECTIVE: The prevalence of reported doctor-diagnosed 'asthma' increased between 1990 and 2005-2007 in Busselton, Western Australia, accompanied by increased reported cough and phlegm but not recent wheeze. Possible reasons for the increase in diagnosed asthma include environmental exposures and diagnostic transfer. The aim of this study was to relate subject characteristics and exposures to the presence of wheeze and/or current cough/phlegm in the 2005-2007 survey. METHODS: A gender- and age-stratified random sample of 2862 adults from the Busselton shire completed questionnaires regarding doctor-diagnosed asthma, respiratory symptoms and environmental exposures; and measures of anthropometry, spirometry, exhaled nitric oxide (eNO), airway hyperresponsiveness (AHR) and atopy. Associations between respiratory symptoms and subject characteristics were assessed in 2656 subjects. RESULTS: Wheeze was reported by 23% of subjects, cough/phlegm by 22% and both by 9%. The significant and independent correlates of wheeze were reflux symptoms, lung function, AHR, eNO, atopy, body mass index and smoking. The significant and independent correlates of cough/phlegm were reflux symptoms, lung function, smoking and dusty job. Subjects more likely to report only wheeze than only cough/phlegm were female, aged <40 years, atopic, had lower percentage predicted forced expiratory volume in one second (FEV1) or higher percentage predicted force vital capacity. CONCLUSIONS: A variety of risk factors was associated with wheeze or cough/phlegm or both. Increased non-allergic exposures may account for increased prevalence of reported cough and phlegm and may contribute to increased reported asthma in adults.

Measuring energy requirements during pulmonary exacerbations of cystic fibrosis using indirect calorimetry.

OBJECTIVE: The energy demands of individuals with cystic fibrosis (CF) vary depending on pancreatic function, body composition, lung function, and clinical status. In clinical practice, predictive equations are used to determine energy requirements yet do not reliably account for these factors. Research regarding energy requirements during CF pulmonary exacerbation (CFPEx) and clinical stability is conflicting. The aim of this study was to investigate potential within-individual changes in measured resting energy expenditure (mREE) using indirect calorimetry (IC) at the commencement and completion of intravenous antibiotic treatment (IVABx) for CFPEx and during clinical stability. Secondary aims were to investigate potential differences between predicted resting energy expenditure (pREE) using Schofield equation and correlations between clinical factors with mREE. METHODS: Body composition using bioimpedance analysis and mREE were conducted at three time points: commencement of IVABx; completion of IVABx; and clinically stable period thereafter. RESULTS: Twenty-eight adults with CF completed at least one valid IC measurement. No significant within-person changes in mREE and body composition parameters were observed across time points. The mREE was positively correlated with fat-free mass (kg; r = 0.6; P = 0.008). The mREE was significantly higher than pREE at all time points with the mREE/pREE ratio elevated at time point 1:118% ± 19.5%; time point 2: 112% ± 13.2%; and time point 3: 122 ± 14.3%. CONCLUSION: The mREE remained stable during CFPEx and clinical stability. The pREE underestimated mREE and application of injury factor adjustment of 110% to 130% could potentially account for this discrepancy. The potential role of IC and body composition in individualizing CF nutritional assessment and prescription requires further exploration.

Telehealth use in Australian cystic fibrosis centers: Clinician experiences.

BACKGROUND: Telehealth has been rapidly adopted by cystic fibrosis (CF) centers and ongoing use in routine CF care is endorsed by CF consumers. However, data describing CF clinician perceptions regarding telehealth are scarce. We aimed to describe clinician experiences and attitudes towards telehealth in CF care among health professionals across Australia. METHODS: CF multidisciplinary health professionals from all CF clinics in Australia were sent an anonymous electronic survey. RESULTS: Eighty-five responses were received representing 15 of 23 (65%) centers. Most clinicians reported using telehealth for routine clinic visits, and a range of other clinical encounters (69.9%). Telehealth was widely perceived as acceptable (91.8%), and clinicians were comfortable/very comfortable (81.2%) integrating telehealth into future CF care. Despite this, 64.1% of respondents considered telehealth clinics to be much worse than face-to-face clinics and 57.5% reported quality of care was somewhat/much worse using telehealth. Home spirometry was available in 73.7% of centers, however, only 26.7% of clinics could provide spirometers for >75% eligible patients. Growth and microbiology assessments were often missed in telehealth clinics and 75.7% reported a technical issue had prevented a telehealth consultation from occurring. CONCLUSIONS: Telehealth for CF in Australia is considered feasible and acceptable by CF clinicians, although use of telehealth varies widely between centers. Concerns exist around the impact of telehealth on health outcomes, especially given core assessments are frequently omitted. Guidelines may help ensure the benefits of telehealth are realized for people with CF without compromising the standard of care.

Role of endobronchial ultrasound in diagnosis and molecular assessment of metastatic melanoma.

BACKGROUND AND OBJECTIVE: Vemurafenib is a new inhibitor of the mutated BRAF oncogene. In the presence of mutated BRAF in metastatic melanoma, treatment with vemurafenib leads to a reduction in mortality and in tumour progression when compared with chemotherapy. This study describes nine cases in which endobronchial ultrasound (EBUS) guided transbronchial needle aspiration (TBNA) was used to assess mediastinal and hilar lymph nodes for the presence of metastatic melanoma and demonstrates the ability to detect mutations in BRAF on the tissue obtained. METHODS: A retrospective review was performed of all patients who had a history of melanoma and underwent EBUS TBNA to investigate hilar or mediastinal lymphadenopathy for the presence of metastatic melanoma. RESULTS: In seven of the nine cases, metastatic melanoma was confirmed on cytology. The two negative cases were proven to be true negatives by follow up or by demonstrating an alternate diagnosis. In five cases, analysis for BRAF mutation was performed. Four cases were positive for mutation and one demonstrated wild-type BRAF. CONCLUSIONS: Tissue samples obtained from EBUS TBNA are adequate to diagnose metastatic melanoma in hilar and mediastinal lymph nodes and to detect the presence or absence of mutations in the BRAF gene. Our findings suggest that close collaboration between bronchoscopists and pathologists will be needed to implement BRAF testing in routine practice in the era of targeted therapy.

Living with cystic fibrosis during the COVID-19 pandemic: a social connectedness perspective.

PURPOSE: This study explores the concept of social connectedness for adults with Cystic Fibrosis (CF), generally and during the onset of the COVID-19 pandemic, to help inform contemporary CF healthcare. Social connectedness is an essential component of belonging and refers to an individual's sense of closeness with the social world. Unique disease factors make exploration of social connectedness pertinent, added to by COVID-19, with the CF population potentially facing increased risk for severe illness. METHODS: Seventeen adults with CF in Western Australia undertook interviews, with findings categorized as overarching themes. RESULTS: In a general sense, participants described social connectedness challenges caused by CF, despite which they reported meaningful connections that benefits their mental and physical health. Within a COVID-19 specific context, participants demonstrated resilience in the face of adversity, highlighted the importance of empathy in relation to the pandemic, and described how social support is both an outcome and enhancer of social connectedness. CONCLUSIONS: This study contributes to limited social connectedness literature within CF and chronic illness in general, highlighting the importance of social connectedness awareness raising, assessments and interventions in CF healthcare inside and outside the COVID-19 pandemic.

Tobramycin safety and efficacy review article.

Pseudomonas aeruginosa is a common respiratory pathogen found in patients with cystic fibrosis (CF), contributing to increased hospitalization, more rapid progression of CF lung disease, and increased risk of death. Guidelines recommend early therapy using tobramycin inhaled solution (TIS) or inhaled powder (TIP). Both TIS and TIP treatment regimens have demonstrated positive clinical outcomes in efficacy and safety, including improvements in FEV1, decreased sputum P. aeruginosa density, decreased rates in antipseudomonal antibiotic use, and reduced rates of hospitalizations due to respiratory events. In a comparison of patient preference for TIS versus TIP, a patient survey cited time savings and convenience as preferences for TIP. However, both TIP and TIS offer advantages that may benefit patients and increase treatment adherence depending on patient circumstances. TIS may be suitable for younger patients at home where parents and caregivers may better control proper administration, older individuals, and those with low FEV1. Dry powder inhalers are suitable when patients have less time to commit to their self-care (eg, patients who work, are remotely located, return home late, or are on vacation), and can reduce the patient treatment burden compared with nebulized delivery. In this expert review, we summarize the available data on tobramycin regarding its molecular characteristics, mechanism of action, and efficacy and safety for the treatment of acute and chronic P. aeruginosa infection.

Survival of people with cystic fibrosis in Australia.

Survival statistics, estimated using data from national cystic fibrosis (CF) registries, inform the CF community and monitor disease progression. This study aimed to estimate survival among people with CF in Australia and to identify factors associated with survival. This population-based cohort study used prospectively collected data from 23 Australian CF centres participating in the Australian CF Data Registry (ACFDR) from 2005-2020. Period survival analysis was used to calculate median age of survival estimates for each 5-year window from 2005-2009 until 2016-2020. The overall median survival was estimated using the Kaplan-Meier method. Between 2005-2020 the ACFDR followed 4,601 people with CF, noting 516 (11.2%) deaths including 195 following lung transplantation. Out of the total sample, more than half (52.5%) were male and 395 (8.6%) had undergone lung transplantation. Two thirds of people with CF (66.1%) were diagnosed before six weeks of age or by newborn/prenatal screening. The overall median age of survival was estimated as 54.0 years (95% CI: 51.0-57.04). Estimated median survival increased from 48.9 years (95% CI: 44.7-53.5) for people with CF born in 2005-2009, to 56.3 years (95% CI: 51.2-60.4) for those born in 2016-2020. Factors independently associated with reduced survival include receiving a lung transplant, having low FEV1pp and BMI. Median survival estimates are increasing in CF in Australia. This likely reflects multiple factors, including newborn screening, improvement in diagnosis, refinements in CF management and centre-based multidisciplinary care.