Emma McNally

Background: Parapneumonic pleural effusions (PPE) range from simple exudates to complex fibrinous collections which fail standard drainage, requiring fibrinolysis or surgery. As recognised contributors to immunothrombosis, understanding the impact of the PPE microenvironment on macrophage thrombin generation is essential. Aim: To define how the PPE microenvironment shapes macrophage phenotype and thrombogenicity. Methods: Pleural fluid (PF) collected from PPE and transudate (TPE) controls was centrifuged to obtain acellular supernatant. PF cytokines were quantified by multiplex ELISA and metabolites by mass spectrometry. Healthy-donor monocyte-derived macrophages (MDM) were incubated with PPE or TPE. Macrophage phenotype was assessed by flow cytometry. Thrombin generation was measured using fluorogenic thrombin assays, sandwich ELISA and chromogenic factor X (FXa) assays. Multiple linear regression tested associations between metabolites and macrophage thrombogenicity. Results: PPE fluid demonstrated a metabolomic profile distinct from transudate, with the top differentially abundant metabolites being lipids. PPE exposure increased macrophage CD163 and CD206 and reduced CD40 expression (p<0.05). PPE fluid enhanced macrophage thrombin generation, with reduced lag time and increased peak thrombin and endogenous thrombin potential (p<0.05). PF Cholesteryl esters significantly correlated with thrombin generation (r=0.838, p=0.03). Conclusion: The PPE microenvironment drives an alternatively activated macrophage phenotype with increased thrombogenic potential. Early findings suggest pleural fluid lipids, particularly cholesteryl esters, contribute to macrophage mediated thrombogenesis. Targeted lipid depletion may represent a therapeutic strategy to reduce fibrin deposition in pleural infection.

Background: Chronic obstructive pulmonary disease (COPD) negatively impacts clinical health outcomes, resulting in frequent exacerbations, increased hospitalizations, reduced physical activity, deteriorated quality of life, and diminished self-efficacy. Previous studies demonstrated that a self-management program tailored for adults with COPD improves self-management decisions, resulting in a positive effect on clinical health outcomes. Limitations of these studies include issues regarding heterogeneity among interventions used, patient population characteristics, outcome measures, and longitudinal studies. Limited studies focused on the use of a comprehensive self-management program using a smartphone app for adults with COPD over 12 months. Objective: This study aimed to explore the effectiveness of a smartphone app self-management program and monthly phone calls compared with standard respiratory outpatient care on clinical health outcomes in adults with COPD. Methods: This was a 3-arm parallel pilot randomized controlled trial (RCT) that included 92 participants. Participants were randomized into intervention arm 1, which included a self-management smartphone app and monthly phone calls (n=31); intervention arm 2, which included a self-management smartphone app (n=31); and arm 3, which was standard respiratory outpatient care (n=30). All arms received standard respiratory outpatient care. The primary outcome was a binary indicator equal to 1 if participants reported attendance to a general practitioner (GP) and or a hospital setting as a result of an exacerbation and 0 otherwise. This indicator was recorded at 6 months and 12 months from the baseline. Secondary outcomes included engagement, breathlessness, physical activity, health-related quality of life, and self-efficacy. Results: There was a statistically significant difference (P=.03), indicating fewer exacerbations in the intervention arm 2 compared with the control arm at 6 months in the hospital setting. The intervention arms had a statistically significant difference indicating a lower risk of developing an exacerbation at 6 months in both the GP (P=.01) and hospital setting (P=.006) compared to the control arm. Furthermore, intervention arm 1 demonstrated a statistically significant difference in exercise capacity at 6 and 12 months (P=.02 and P=.03). The intervention arm 2 illustrated a statistically significant difference in step count (P=.009) compared to the control arm. The majority of participants (60%, 33/55) used the app over the 12-month period. Conclusions: This study demonstrated that a smartphone app self-management program had a positive effect on clinical health outcomes for participants with COPD in comparison to standard respiratory outpatient care. This study illustrated benefits such as reduced exacerbations resulting in fewer hospitalizations, improved exercise capacity, and physical activity among the intervention arms. This was a single-center study, which was limited in power to demonstrate significant effects on all measured outcomes but paves the way for a larger, fully powered multicenter trial exploring the effect of a smartphone app self-management program on clinical health outcomes in adults with COPD. Trial Registration: ClinicalTrials.gov NCT05061810; https://clinicaltrials.gov/study/NCT05061810

BACKGROUND Chronic obstructive pulmonary disease (COPD) negatively impacts clinical health outcomes, resulting in frequent exacerbations, increased hospitalizations, reduced physical activity, deteriorated quality of life, and diminished self-efficacy. Previous studies demonstrated that a self-management program tailored for adults with COPD improves self-management decisions, resulting in a positive effect on clinical health outcomes. Limitations of these studies include issues regarding heterogeneity among interventions used, patient population characteristics, outcome measures, and longitudinal studies. Limited studies focused on the use of a comprehensive self-management program using a smartphone app for adults with COPD over 12 months. OBJECTIVE This study aimed to explore the effectiveness of a smartphone app self-management program and monthly phone calls compared with standard respiratory outpatient care on clinical health outcomes in adults with COPD. METHODS This was a 3-arm parallel pilot randomized controlled trial (RCT) that included 92 participants. Participants were randomized into intervention arm 1, which included a self-management smartphone app and monthly phone calls (n=31); intervention arm 2, which included a self-management smartphone app (n=31); and arm 3, which was standard respiratory outpatient care (n=30). All arms received standard respiratory outpatient care. The primary outcome was a binary indicator equal to 1 if participants reported attendance to a general practitioner (GP) and or a hospital setting as a result of an exacerbation and 0 otherwise. This indicator was recorded at 6 months and 12 months from the baseline. Secondary outcomes included engagement, breathlessness, physical activity, health-related quality of life, and self-efficacy. RESULTS There was a statistically significant difference (P=.03), indicating fewer exacerbations in the intervention arm 2 compared with the control arm at 6 months in the hospital setting. The intervention arms had a statistically significant difference indicating a lower risk of developing an exacerbation at 6 months in both the GP (P=.01) and hospital setting (P=.006) compared to the control arm. Furthermore, intervention arm 1 demonstrated a statistically significant difference in exercise capacity at 6 and 12 months (P=.02 and P=.03). The intervention arm 2 illustrated a statistically significant difference in step count (P=.009) compared to the control arm. The majority of participants (60%, 33/55) used the app over the 12-month period. CONCLUSIONS This study demonstrated that a smartphone app self-management program had a positive effect on clinical health outcomes for participants with COPD in comparison to standard respiratory outpatient care. This study illustrated benefits such as reduced exacerbations resulting in fewer hospitalizations, improved exercise capacity, and physical activity among the intervention arms. This was a single-center study, which was limited in power to demonstrate significant effects on all measured outcomes but paves the way for a larger, fully powered multicenter trial exploring the effect of a smartphone app self-management program on clinical health outcomes in adults with COPD. CLINICALTRIAL ClinicalTrials.gov NCT05061810; https://clinicaltrials.gov/study/NCT05061810

Pleural tuberculosis (TB) is a common entity with similar epidemiological characteristics to pulmonary TB. It represents a spectrum of disease that can variably self-resolve or progress to TB empyema with severe sequelae such as chronic fibrothorax or empyema necessitans. Coexistence of and progression to pulmonary TB is high. Diagnosis is challenging, as pleural TB is paucibacillary in most cases, but every effort should be made to obtain microbiological diagnosis, especially where drug resistance is suspected. Much attention has been focussed on adjunctive investigations to support diagnosis, but clinicians must be aware that apparent diagnostic accuracy is affected both by the underlying TB prevalence in the population, and by the diagnostic standard against which the specified investigation is being evaluated. Pharmacological treatment of pleural TB is similar to that of pulmonary TB, but penetration of the pleural space may be suboptimal in complicated effusions. Evidence for routine drainage is limited, but evacuation of the pleural space is indicated in complicated disease.Educational aims: To demonstrate that pleural TB incorporates a wide spectrum of disease, ranging from self-resolving lymphocytic effusions to severe TB empyema with serious sequelae. To emphasise the high coexistence of pulmonary TB with pleural TB, and the importance of obtaining sputum for culture (induced if necessary) in all cases. To explore the significant diagnostic challenges posed by pleural TB, and consequently the frequent lack of information about drug sensitivity prior to initiating treatment. To highlight the influence of underlying TB prevalence in the population on the diagnostic accuracy of adjunctive investigations for the diagnosis of pleural TB. To discuss concerns around penetration of anti-TB medications into the pleural space and how this can influence decisions around treatment duration in practice.

Acute fibrinous and organising pneumonia (AFOP) is a rare form of interstitial lung disease. It is a pathological diagnosis sharing similarities to organising pneumonia, diffuse alveolar damage and eosinophilic pneumonia, however, is histologically distinct, characterised by intra-alveolar fibrin deposition (‘fibrin balls’) and associated organising pneumonia. AFOP was first described in 2002, only 150 cases have been reported since. While it has been described in association with infection, autoimmune disorders, connective tissue diseases, drugs, environmental exposures and organ transplant, it can also be idiopathic in nature. AFOP follows an acute course with potential rapid fulminant respiratory failure, or a subacute trajectory with a more favourable prognosis. Corticosteroids are commonly prescribed to induce remission. While cases of relapse of AFOP during weaning or cessation of steroids have been described, there are no published cases of remote relapse of AFOP. We describe a case of idiopathic AFOP, which recurred after 12 years of good health.

Pulmonary mucosa-associated lymphoid tissue (pMALT) lymphomas are rare, representing 80%. Thus, an index of suspicion and early detection are vital. This case highlights that pMALT should be considered in patients with non-specific symptoms and coeliac disease. Bronchoscopy is a valuable diagnostic tool to be used in these cases.