Patterns of Disease in Patients with Middle-Lobe Predominant Bronchiectasis.

BACKGROUND: Middle-lobe predominant bronchiectasis affecting the right middle-lobe and/or lingula (RMLP) is classically described in asthenic, elderly females with skeletal abnormalities or associated nontuberculous mycobacterial (NTM) infection. OBJECTIVES: We aimed to evaluate the frequency and clinical characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed bronchiectasis patients and determine associations with disease severity. METHODS: A retrospective observational cross-sectional cohort study of consecutive bronchiectasis patients in our institution was performed. Data were collected on baseline variables, microbiology status, lung function, and radiology according to the modified Bhalla score. Disease severity was assessed using bronchiectasis severity index (BSI) and FACED severity scores. RESULTS: Of 81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20 (24.7%) had RMLP disease. These patients were significantly younger, female, and with lower BMIs than patients with the classical bronchiectasis phenotype (p = 0.03, 0.01, and p <0.01, respectively). Fewer symptoms of cough and daily sputum (p = 0.01 and <0.01), prior exacerbation frequency (p = 0.03), and higher baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in RMLP patients were significantly lower than their counterparts (both p < 0.001). CONCLUSIONS: The RMLP phenotype is associated with younger patients than classically described in the literature. An increased rate of NTM infection in this phenotype was noted, particularly in females, but much lower than previously described. Lung function and disease severity scores in this patient group are relatively normal, suggesting a milder phenotype in patients with this form of the disease.

Hiatal hernias are correlated with increased severity of non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Hiatal hernias (HH) are associated with gastro-oesophageal reflux and may contribute to lung disease severity. We aimed to evaluate the prevalence of HH among stable non-cystic fibrosis bronchiectasis (NCFB) patients and determine associations with disease severity. METHODS: A retrospective cross-sectional cohort study of 100 consecutive NCFB patients in our institution was performed. Data were collected on baseline variables, microbiology, lung function and radiology, according to the modified Bhalla score. Disease severity was assessed using the Bronchiectasis Severity Index (BSI) and FACED severity scores. RESULTS: Following expert radiological review, 81 patients were deemed suitable for study inclusion (mean age (SD) 62.6 (12.4), females 55 (67.9%), body mass index (BMI) 26.9 (5.7)); 29 (35.8%) were HH positive (HH+). HH+ patients had a trend towards higher BMI (P = 0.07), and a significantly higher proportion had reflux symptoms (HH+ 62.1% vs HH- 28.8%, P < 0.01). The presence of HH+ was associated with cystic bronchiectasis (HH+ 30.1%, HH- 11.5%; P = 0.03), increased number of lobes involved (HH+ 2.62 (1.54), HH- 2.17 (1.42); P = 0.03), increased extent of bronchiectasis, (HH+ 6.2 (4.7), HH- 4.5 (3.1); P = 0.04), decreased parenchymal attenuation (HH+ 1.0 (1.8), HH- 0.2 (0.5); P = 0.03) and reduced per cent predicted forced expiratory volume in 1 s (HH+ 75.4% (24.5), HH- 90.4% (25.5); P = 0.02). There was no lobar predilection. HH+ was associated with increased disease severity scores: BSI (HH+ 4.93 (1.65), HH- 3.25 (2.13); P < 0.001) and FACED (HH+ 2.21 (1.52), HH- 1.35 (1.43); P < 0.01). CONCLUSIONS: HH+ was associated with worse disease severity in NCFB patients, characterized by decreased lung function, increased extent and severity of radiological disease, and increased composite disease severity scores.

Posterior pharyngeal candidiasis in the absence of clinically overt oral involvement: a cross-sectional study.

PURPOSE: Although oropharyngeal candidiasis is associated with inhaled corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior pharyngeal candidiasis in those without any detectable oral candidiasis on clinical examination. We systematically investigated the relationship between oral candidiasis on clinical examination and the presence of posterior pharyngeal candidiasis at bronchoscopy. METHODS: We conducted a cross-sectional study on a convenience sample of 100 patients undergoing bronchoscopy at our institution. Patients were assessed for symptoms of and risk factors for candida infection and had an examination of their oropharynx for evidence of candidiasis before bronchoscopy. They subsequently had a detailed assessment for posterior candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which focused solely on those patients on ICS maintenance therapy. RESULTS: Median age was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS, and 20 % of this cohort received recent oral corticosteroids. Twenty-eight percent of this convenience sample had posterior pharyngeal candidiasis; however, only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis on clinical examination before bronchoscopy. Factors that were independently associated with the presence of pharyngeal candidiasis at bronchoscopy were OR (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62-17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of ICS usage, posterior pharyngeal candidiasis was correlated with the presence of dysphonia but was not independently associated with fluticasone or budesonide dosage. CONCLUSIONS: This study demonstrates that posterior pharyngeal candidiasis in the absence of clinically overt oral candidiasis is frequent amongst ICS users. A history of ICS use, particularly fluticasone usage, as well as the presence of dysphonia are associated with posterior pharyngeal candidiasis at bronchoscopy, even in the absence of clinically overt oral involvement.

A cross-sectional survey of doctors' views on flexible postgraduate physician training in Ireland.

Recruitment and retention of doctors is a priority for the Irish healthcare service, with many leaving to work in regions with more favourable conditions. Aligning flexible training options with other jurisdictions may be an effective means of improving working conditions. We sought to assess possible improvements to the existing system and to review barriers to flexible training. We carried out a survey using 'Survey Monkey' and disseminated it to 1557 basic specialist (BST) and higher specialist trainee (HST) doctors of the Institute of Medicine, 3500 members of the Irish Medical Organisation (IMO), and across social media. There were 854 respondents; 303 (35.5%) BST, 352 (41.2%) HST, 125 (14.6%) non-training doctors, unknown, n = 74. The response rate was approximately 15-23%. Non-consultant doctors identified a preference for access to flexible training (n = 849, 99.4%), with 82.2 of doctors reporting that they would consider applying (n = 702). Most (92.4%) considered the current provision of 16 whole-time equivalent positions as inadequate (n = 789). Of doctors who would not apply for flexible training, themes identified included a perceived negative impact on their career, not meeting eligibility criteria, prolonged training, and salary implications. Suggestions for improving the system included expanding the number of places available, removing eligibility criteria, job sharing options, and the provision of regional training schemes. Access to flexible training should be a priority for the healthcare service, which may enhance recruitment and retention. A majority of our sample of non-consultant doctors identified a preference for access to flexible training options.

Symptoms to script: delays in tuberculosis treatment in the west of Ireland.

BACKGROUND: The first pillar of the End-TB Strategy is "early diagnosis and prompt treatment". Nevertheless, long delays in starting tuberculosis (TB) treatment are reported. We aimed to describe the demographics and clinical features of TB in the west of Ireland and better understand the delays in treatment. METHODS: We conducted a retrospective chart review of all patients diagnosed with active TB who attended the Galway University Hospital (GUH) TB clinic from 2014 to 2018. RESULTS: Eighty-five patients were diagnosed with TB and attended our clinic. Ten (12%) patients were receiving immunosuppressive therapy, 8 (9%) had drug resistance, and 41 (48%) had extra-pulmonary disease. Patients with extra-pulmonary disease had a longer length of stay before treatment (11 vs. 4 days; p = 0.006). Patients older than 55 had a longer length of stay before (16 vs. 5 days, p = 0.0001) and during (36 vs. 11 days, p = 0.004) treatment and were readmitted more frequently than younger patients. A total of 36% of patients were born outside Ireland. Non-Irish patients were younger (mean age 35 vs 48; p = 0.004) and more frequently had drug resistance (19% vs. 4%, p = 0.02). The median time from symptom onset to hospital presentation was 76 days (IQR 35-146 days) and the median time from first hospital presentation to TB treatment was 11 days (IQR 5-51 days). CONCLUSION: TB patients experienced long symptom durations in the community prior to presentation. Many TB patients experienced delays in diagnosis and treatment following presentation. Both pre-hospital and in-hospital delays need to be addressed in order to 'End-TB'.

Therapeutic implications of ongoing alveolar viral replication in COVID-19.

In patients with moderate-to-severe COVID-19 pneumonia, an aberrant post-viral alveolitis with excessive inflammatory responses and immunothrombosis underpins use of immunomodulatory therapy (eg, corticosteroids and interleukin-6 receptor antagonism). By contrast, immunosuppression in individuals with mild COVID-19 who do not require oxygen therapy or in those with critical disease undergoing prolonged ventilation is of no proven benefit. Furthermore, a window of opportunity is thought to exist for timely immunosuppression in patients with moderate-to-severe COVID-19 pneumonia shortly after clinical presentation. In this Viewpoint, we explore the shortcomings of a universal immunosuppression approach in patients with moderate-to-severe COVID-19 due to disease heterogeneity related to ongoing SARS-CoV-2 replication, which can manifest as RNAaemia in some patients treated with immunotherapy. By contrast, immunomodulatory therapy has overall benefits in patients with rapid SARS-CoV-2 clearance, via blunting of multifaceted, excessive innate immune responses in the lungs, potentially uncontrolled T-cell responses, possible autoimmune responses, and immunothrombosis. We highlight this therapeutic dichotomy to better understand the immunopathology of moderate-to-severe COVID-19, particularly the role of RNAaemia, and to refine therapy choices.

The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease.

Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

Mycobacterium goodii pneumonia: An unusual presentation of nontuberculous mycobacterial infection requiring a novel multidisciplinary approach to management.

BACKGROUND: Mycobacterium goodii is a rapidly growing nontuberculous mycobacterium which has been associated with several infections including cellulitis, osteomyelitis, lymphadenitis, infected pacemakers and bursitis but it is a rare cause of respiratory infection. CASE PRESENTATION: In this case report we describe a 51-year-old woman who presented with a 6-week history of non-productive cough, pleuritic chest pain and weight loss. She had a history of gastric adenocarcinoma managed with a distal oesophagectomy and total gastrectomy and consequentially suffered severe post-operative gastric reflux. Initial cultures were negative but following a VATS lung biopsy Mycobacterium goodii was cultured and histology revealed an organising pneumonia. Treatment was with a prolonged course of steroids, amikacin and meropenem followed by oral ciprofloxacin and doxycycline. Ongoing gastric dysmotility and weight loss showed clinical improvement with a novel approach of a combination of prokinetics and somatostatin analogues controlling risk of repeat aspiration and improving symptom control. CONCLUSIONS: This is an unusual case of organising pneumonia related to Mycobacterium goodii infection and highlights the importance of mycobacterial culture in unusual and unresolving cases of organising pneumonia. The importance of controlling symptoms related to gastric dysmotility and aspiration is also addressed.

When your immune system falls out with your heart: an important lesson on antisynthetase myocarditis.

A 57-year-old special Olympics athlete presented with subacute onset dyspnoea. Baseline investigations revealed troponin T rise and an abnormal ECG, which prompted coronary angiography. This was unremarkable, as was his transthoracic echocardiography (TTE). He re-presented 7 months later with progressive dyspnoea associated with significant weight loss, peripheral oedema and intermittent fevers. Examination revealed bilateral fine end-inspiratory crackles, peripheral oedema and fever. Investigations revealed elevated troponin T and raised inflammatory markers. ECG remained unchanged, whereas TTE revealed mild global impairment of left ventricular function. Chest radiography was suggestive of extensive interstitial lung disease, which was confirmed by high resolution CT. Presence of interstitial lung disease and myocarditis raised the suspicion of a systemic inflammatory condition. Subsequently, an autoimmune screen was positive for anti-Jo-1 antibody associated with antisynthetase syndrome. He was treated with high-dose steroids and rituximab with dramatic symptomatic improvement and immediate fall in troponin T level.

The role of osteopontin in lung disease.

Osteopontin (Opn) is a multifunctional protein independently discovered by investigators from diverse scientific backgrounds and implicated in a broad array of pathological processes. Opn exists both intra- and extracellularly and in numerous pre- and post-translational isoforms. Structurally Opn resembles a matrix protein yet it has well-characterized cytokine like properties including the regulation of cellular migration and cell-mediated immunity. It has thus been classified as both a matricellular protein and a cytokine. Opn is among the most abundantly expressed proteins in a range of lung diseases and has been shown to regulate aspects of pulmonary granuloma formation, fibrosis, and malignancy. Future studies will explore the diagnostic and therapeutic potential of modulating the function of Opn in vivo.

Predictive value of C-reactive protein and clinically relevant baseline variables in sarcoidosis.

BACKGROUND: This study aims to examine the predictive and prognostic implications of C-reactive protein (CRP) and clinically relevant baseline variables in determining treatment indication and disease progression in a large clinical cohort of patients with stable sarcoidosis. METHODS: A retrospective observational study of 328 sarcoidosis patients attending a regional tertiary referral centre over a 26-year period was performed. Clinical, biochemical, radiological and physiological data were analysed according to a clinically relevant dichotomous cutpoint of CRP. Multiple models of logistic regression were used to determine independent predictors of outcome as defined by indication for treatment with corticosteroids, radiological deterioration and physiological progression. RESULTS: 328/409 (80.2%) sarcoidosis patients had baseline serum CRP measured and were suitable for inclusion. Baseline CRP was elevated in 154 (47%). 178 (54.3%) were prescribed corticosteroid treatment during the disease course. Physiological deterioration was demonstrated in 48 (14.6%) patients and radiological progression in 59 (17.9%) patients. High baseline CRP was strongly associated with Lofgren's syndrome (p=<0.001) and reduced FVC% predicted (p=0.012). High CRP was found to be a negative predictor of radiological progression (p=0.046). In a sub-analyses of patients without Lofgren's syndrome (n=223), patients with high baseline CRP were almost twice as likely to receive corticosteroid treatment, OR 1.89 (95% CI 1.04-3.55). Low baseline DLCO% independently predicted the need for corticosteroid treatment (p=<0.001) and physiological decline (p=0.045). CONCLUSIONS: Elevated baseline CRP in sarcoidosis is associated with a good prognosis and is a negative predictive indicator of radiological progression. In patients without Lofgren's syndrome, high CRP and low DLCO% at presentation may identify a subset of patients more likely to develop physiological progression who may benefit from early systemic treatment.

High prevalence of obstructive lung disease in non-smoking farmers: The Irish farmers lung health study.

BACKGROUND: Mortality rates within the Irish farming community are increasing, whilst that of the general population falls. The aim of this cross-sectional study was to determine the prevalence of respiratory disease amongst Irish farmers. METHODS: All study participants were farming volunteers attending an agricultural exhibition. Data collected by questionnaire included baseline demographics, respiratory history, presence of respiratory symptoms and occupational exposures. Spirometry was performed on all participants. RESULTS: Data from 372 farmers was analysed. The majority were male (76%) with median age of 55 years. 61% were never smokers. 13% were previously diagnosed with airway disease (Chronic Obstructive Pulmonary Disease(COPD)/Asthma/Inhaler use) with 14% reporting hayfever/allergies. Almost two-thirds reported one or more chronic respiratory symptom. Forty-four (12%) had obstructive spirometry using fixed FEV1/FVC < 0.70 criterion and 29 (7.8%) using FEV1/FVC < 5% lower limit of normal. The majority, two-thirds, were never smokers. Amongst never smokers with obstruction (13%), there was a significantly higher proportion with a prior diagnosis of airway disease and hayfever/allergies. There was no significant association between specific occupational exposures and obstruction. CONCLUSION: The majority of Irish farmers are never smokers. They have a high prevalence of respiratory symptoms. 13% of never smokers have airflow obstruction (FEV1/FVC < 0.70). The presence of airflow obstruction is significantly associated with self-reported allergy history and prior airway disease. Further studies are needed to identify the workplace factors accounting for these findings.