ERS Statement on Benign Pleural Effusions in Adults.

The incidence of non-malignant pleural effusions (NMPE) far outweighs that of malignant pleural effusions (MPE) and is estimated to be at least 3-fold higher. These so called "benign" effusions do not follow a "benign course" in many cases, with mortality rates matching and sometimes exceeding that of MPEs. In addition to the impact on patients, healthcare systems are significantly affected, with recent US epidemiological data demonstrating that 75% of resource allocation for pleural effusion management is spent on NMPEs (excluding empyema). Despite this significant burden of disease, and by existing at the junction of multiple medical specialties, reflecting a heterogenous constellation of medical conditions, NMPEs are rarely the focus of research or the subject of management guidelines. With this ERS Taskforce, we assembled a multi-specialty collaborative across eleven countries and three continents to provide a Statement based on systematic searches of the medical literature to highlight evidence in the management of the following clinical areas: a diagnostic approach to transudative effusions, heart failure, hepatic hydrothorax, end stage renal failure, benign asbestos related pleural effusion, post-surgical effusion and non-specific pleuritis.

Does bronchial hyperresponsiveness predict a diagnosis of cough variant asthma in adults with chronic cough: a cohort study.

Bronchial hyperresponsiveness is a typical, but non-specific feature of cough variant asthma (CVA). This study aimed to determine whether bronchial hyperresponsiveness may be considered as a predictor of CVA in non-smoking adults with chronic cough (CC). The study included 55 patients with CC and bronchial hyperresponsiveness confirmed in the methacholine provocation test, in whom an anti-asthmatic, gradually intensified treatment was introduced. The diagnosis of CVA was established if the improvement in cough severity and cough-related quality of life in LCQ were noted.The study showed a high positive predictive value of bronchial hyperresponsiveness in this population. Cough severity and cough related quality of life were not related to the severity of bronchial hyperresponsiveness in CVA patients. A poor treatment outcome was related to a low baseline capsaicin threshold and the occurrence of gastroesophageal reflux-related symptoms. In conclusion, bronchial hyperresponsiveness could be considered as a predictor of cough variant asthma in non-smoking adults with CC.

Expression of TSLP and IL-33 receptors on sputum macrophages of asthma patients and healthy subjects.

Objective: Local cytokine milieu (especially Th2 inflammatory type) secreted into the asthmatic airways affect the alternative activated macrophages polarization (M2). TSLP and IL-33 are important alarmins of allergic response associated with Th2 inflammation. The aim of the study was to investigate the expression of the receptors for epithelial derived cytokines: TSLP (TSLPR) and IL-33 (ST2) on induced sputum CD206 positive macrophages from asthma and healthy subjects and analyze the relationships between these receptors and clinical features of the disease. Methods: Immunofluorescence staining for CD206 and TSLPR or ST2 on sputum macrophages was performed in 20 adult patients with stable asthma - 75% with atopy (3 intermittent, 12 mild-to-moderate, 5 severe, of which 11 were on biological anty-IgE treatment) and 23 healthy adult controls - 48% with atopy. Results: Our study demonstrated an increased expression of TSLP and IL-33 receptors on bronchial CD206 positive macrophages in asthma group. TSLPR but not ST2 had also greater expression on CD206 negative macrophages in asthma patients. Increased expression of both investigated receptors was related to longer disease duration and impaired lung function. We observed increased count of CD206lowTSLPhigh macrophages as well as positive correlation of these cells with total serum IgE in patients with atopy. Conclusions: The macrophage response during allergic reaction is likely to be connected with TSLP but rather not with IL-33 action. Our study indicates an important role of crosstalk between macrophages, TSLP and IL-33 in asthma pathophysiology.

Chronic cough related to the upper airway cough syndrome: one entity but not always the same.

PURPOSE: Upper airway cough syndrome (UACS), described as chronic cough (CC) associated with allergic (AR), non-allergic rhinitis (NAR) or chronic rhinosinusitis (CRS), is one of the major causes of CC. We aimed to characterize a cohort of UACS patients with special attention to differences between patients with AR and NAR. METHODS: A prospective analysis of clinical data of patients, diagnosed with UACS between 2015 and 2018. RESULTS: There were 143 patients diagnosed with UACS, median age 52 years, women predominance (68.5%), The group comprised of 59 (41%) AR and 84 (59%) NAR subjects, CRS diagnosed in 17 (12%). Median cough duration: 48 months (IQR 24-120), median cough severity (VAS)-60 mm (IQR 42-78), median Leicester Cough Questionnaire (LCQ) score-11.3 (IQR 8.7-13.7), never-smokers: 70%. The most common symptoms: PND (62%), rhinorrhea (59%), nasal congestion (54%), abnormalities of sinus CT: septum deviation (62%), turbinates hypertrophy (53%), mucosal thickening (53%). UACS as the only cause of CC, was presented in 20 patients (14%). We found no differences between patients with AR and NAR in terms of age, gender, duration and severity of cough, BMI, blood eosinophil count, total IgE and FeNO. AR was associated with higher comorbidity of asthma than NAR (54% vs 35%, p = 0.019). Abnormalities in sinus CT scan were more frequently found in patients with NAR than AR (p = 0.018). CONCLUSION: NAR is the most common upper airway disease associated with UACS. Clinical characteristics of UACS patients with AR and NAR are similar with only minor differences between these groups. It seems reasonable to plan further studies concerning relationship of NAR and cough sensitivity, also in terms of potential similar neurogenic mechanism.

Patterns of pleural pressure amplitude and respiratory rate changes during therapeutic thoracentesis.

BACKGROUND: Although the impact of therapeutic thoracentesis on lung function and blood gases has been evaluated in several studies, some physiological aspects of pleural fluid withdrawal remain unknown. The aim of the study was to assess the changes in pleural pressure amplitude (Pplampl) during the respiratory cycle and respiratory rate (RR) in patients undergoing pleural fluid withdrawal. METHODS: The study included 23 patients with symptomatic pleural effusion. Baseline pleural pressure curves were registered with a digital electronic manometer. Then, the registrations were repeated after the withdrawal of consecutive portions of pleural fluid (200 ml up to 1000 ml and 100 ml above 1000 ml). In all patients the pleural pressure curves were analyzed in five points, at 0, 25%, 50%, 75% and 100% of the relative volume of pleural effusion withdrawn in particular patients. RESULTS: There were 11 and 12 patients with right sided and left sided pleural effusion, respectively (14 M, 9F, median age 68, range 46-85 years). The most common cause of pleural effusion were malignancies (20 pts., 87%). The median total volume of withdrawn pleural fluid was 1800 (IQR 1500-2400) ml. After termination of pleural fluid withdrawal Pplampl increased in 22/23 patients compared to baseline. The median Pplampl increased from 3.4 (2.4-5.9) cmH2O to 10.7 (8.1-15.6) cmH2O (p < 0.0001). Three patterns of Pplampl changes were identified. Although the patterns of RR changes were more diversified, a significant increase between RR at baseline and the last measurement point was found (p = 0.0097). CONCLUSIONS: In conclusion, therapeutic thoracentesis is associated with significant changes in Pplampl during the respiratory cycle. In the vast majority of patients Pplampl increased steadily during pleural fluid withdrawal. There was also an increase in RR. The significance of these changes should be elucidated in further studies. TRIAL REGISTRATION: ClinicalTrial.gov, registration number: NCT02192138 , registration date: July 1st, 2014.

Sputum interleukin-25 correlates with asthma severity: a preliminary study.

INTRODUCTION: Interleukin 25 is an epithelial-derived cytokine associated with allergic Th2 inflammation. However, little is known about the role of IL-25 in different asthma phenotypes and its relationship with disease severity. AIM: To evaluate and compare the mRNA and protein expression of IL-25 in patients with mild-to moderate/severe asthma and cough variant asthma (CVA). MATERIAL AND METHODS: Thirty-eight patients with stable asthma (11 patients with mild-to-moderate asthma, 14 patients with severe asthma and 13 patients with CVA) and 14 control subjects were enrolled. IL-25 protein concentration was measured in induced sputum (IS) supernatants by ELISA and IL-25 mRNA expression was evaluated in IS cells by real time PCR. RESULTS: No differences in IS IL-25 mRNA and IL-25 concentration between controls and the whole asthma group were found. In the detailed analysis, a lower IL-25 mRNA expression in sputum cells was observed in severe asthma compared to CVA and controls. IL-25 protein concentration in sputum supernatants was elevated in patients with severe asthma compared to controls, CVA and mild-to-moderate asthma. A sputum IL-25 level was increased in atopic vs. non-atopic asthma patients. The elevated IL-25 mRNA expression and protein concentration was associated with a lower eosinophil and higher neutrophil percentage in asthmatic airways. CONCLUSIONS: Our results suggest that IL-25 is particularly associated with severe asthma. The relationship between IL-25 and neutrophilic airway inflammation suggests the pleiotropic role of IL-25 in the immune response in this disease.

Cough during therapeutic thoracentesis: friend or foe?

We report intriguing preliminary observations on the effect of cough on pleural pressure changes during therapeutic thoracentesis. We found that cough-related elevation of pleural pressure persisted even when the cough had stopped. Thus, we hypothesize that cough during therapeutic thoracentesis may have a beneficial effect preventing the excessive drop in pleural pressure. The true role of cough-related elevation of pleural pressure is unknown, but it seems to be an interesting subject for further research.

The utility of oesophageal pH monitoring in diagnosing gastroesophageal reflux disease-related chronic cough.

INTRODUCTION: Chronic cough is a common medical complaint, which may deteriorate patients' quality of life and cause many complications. Gastroesophageal reflux disease (GERD) is one of the frequent reasons for chronic cough. Oesophageal pH monitoring is one of the diagnostic methods performed to confirm diagnosis of GERD-related cough. The aim of the study was to analyse the utility of oesophageal pH monitoring in diagnosing GERD-related cough and to identify the most sensitive pH monitoring parameters for diagnosing GERD-related cough. MATERIAL AND METHODS: 24-hour oesophageal pH monitoring was performed in 204 patients suffering from chronic cough. The group consisted of 65% females and the median age was 59 years. An acid reflux episode was defined as a rapid drop in pH to a value below 4 for at least 12 seconds. The diagnosis of GERD was based on total fraction time of pH < 4, upright or supine fraction time of pH < 4, or DeMeester score. The diagnosis of GERD-related cough was made if cough episodes, marked by the patients, appeared within 2 minutes after the reflux. The association between reflux episode and appearance of cough was analysed using two parameters: symptom index (SI ≥ 50%) and/or symptom association probability (SAP ≥ 95%). RESULTS: Based on results of pH monitoring, 135 patients (135/204, 66%) were diagnosed with GERD. Among them, 117 patients (117/135, 87%) were diagnosed based on DeMeester score. Among patients with GERD, 61 patients met the criteria of GERD-related cough (61/135, 45%), i.e. 30% of the group as a whole. Thirty-six patients (36/61, 59%) were diagnosed based on SAP, 12 patients (20%) based on SI, and 13 (21%) based on both parameters. Spearman rank correlation coefficient for SAP ≥ 95% and SI ≥ 50% was 0.46 (p < 0.05). CONCLUSIONS: Based on pH monitoring results, GERD was diagnosed twice as often as GERD-related cough. SAP index is more sensitive than SI for the diagnosis of GERD-related cough.

Prevalence of refractory and unexplained chronic cough in adults treated in cough centre.

Background: Refractory chronic cough and unexplained chronic cough pose significant clinical challenges, impairing patients' quality of life. However, a precise definition of refractory chronic cough remains elusive. This study aimed to assess the prevalence of refractory and unexplained chronic cough among patients referred to our cough centre and to analyse the prevalence of refractory chronic cough relative to its definition. Methods: This prospective cohort study included all patients who were diagnosed at a cough clinic between 2018 and 2022. The response to therapy was measured based on reduction in cough severity (via a visual analogue scale) and improvement in cough-related quality of life (via the Leicester Cough Questionnaire). Refractory chronic cough was defined as persistent cough severity, with no or minimal improvement (change in visual analogue scale <30 mm) after two or more treatment attempts and cough severity ≥40 out of 100 mm on the visual analogue scale. Results: Of 201 patients treated for chronic cough, only three (1.5%) were diagnosed with unexplained chronic cough. Among 166 patients monitored for therapy response, 71 (42.8%) experienced a cough severity reduction of ≥30 mm on the visual analogue scale, while 100 (60.2%) showed an improvement of ≥1.5 points on the Leicester Cough Questionnaire. Based on the basic refractory chronic cough definition, 51 of 166 patients (30.7%) were diagnosed with refractory chronic cough. If applying stricter criteria (persistent severe cough (≥40 mm on the visual analogue scale), insufficient therapy response (<30 mm reduction on the visual analogue scale) and <1.5-point improvement on the Leicester Cough Questionnaire), 45 of 166 patients (27.1%) would be diagnosed with refractory chronic cough. Conclusions: Refractory chronic cough is common in patients referred to cough clinics. The prevalence of refractory chronic cough differs slightly depending on the diagnostic criteria. Therefore, the definition of refractory chronic cough used in routine practice needs to be clarified.

Imaging of pleural disease.

The pleural space is a "potential" anatomical space which is formed of two layers: visceral and parietal. It normally contains a trace of fluid (∼10 mL in each hemithorax). Diseases of the pleura can manifest with thickening of the pleural membranes or by abnormal accumulation of air or liquid. Chest radiographs are often the first imaging tests to point to a pleural pathology. With the exception of pneumothorax, and due to the inherent limitations of chest radiographs, ultrasound and/or computed tomography are usually required to further characterise the pleural pathology and guide management. This review summarises the utility of different imaging tools in the management of pleural disease and discusses new and evolving tools in imaging of the pleura.

Diagnostic yield of chest radiograph in management of adults with difficult-to-treat chronic cough-retrospective study.

Background: Chest radiograph (CXR) is a routine imaging test in adults with chronic cough (CC), while value of thoracic computed tomography (CT) in these patients is still a matter of discussion. The aims of the study were to assess the diagnostic yield of CXR and to evaluate the impact of thoracic CT on management of patients with difficult-to-treat CC referred to our cough clinic. Methods: The retrospective analysis of paired CXR and CT results was performed in 189 consecutive adults treated due to CC between 2015-2019 in our cough clinic. CC was defined as cough >8 weeks being the main or isolated ailment. The sensitivity, specificity, negative/positive predictive value (NPV, PPV) and diagnostic accuracy of CXR were calculated based on chest CT scan as the "gold standard". Only those CT scans which revealed abnormalities potentially related to CC and were associated with the changes in further diagnostic or therapeutic approach were construed as relevant CT findings during final analysis. Results: The median age of patients (male/female ratio 53/136) was 58 years (IQR 44-67), only 6 subjects (3.0%) were active smokers, median CC duration was 48 months (IQR 24-120). CXR revealed abnormal findings in 23/189 (12.2%) patients. Normal CXR was confirmed by CT in 141 subjects (141/166; 84.9%). In 25/166 (15.1%) patients, CT showed abnormalities that could explain the cause of CC and changed either the diagnostic protocol or therapy. In patients with abnormal CXR, CT confirmed abnormal findings in 8 cases (8/23, 34.8%). The sensitivity, specificity, PPV, NPV, diagnostic accuracy were 24.2%, 90.4%, 34.8%, 84.9% and 78.8%, respectively. Conclusions: CXR shows a limited diagnostic yield in adults with difficult-to-treat CC referred to cough clinic. Chest CT scan may add significant data impacting the diagnostic and therapeutic approach in these patients.

Does hiatal hernia impact gastro-oesophageal reflux-related chronic cough?

Background: Hiatal hernia may coexist with gastro-oesophageal reflux (GOR)-related chronic cough. This study aimed to evaluate whether the presence of hiatal hernia was related to chronic cough severity and the response to antireflux therapy. Methods: This was a retrospective analysis of data on adults with GOR-related chronic cough managed in our cough centre between 2017 and 2021. Patients who had undergone chest computed tomography (CT) and in whom follow-up data were available were included. The presence and size of hiatal hernia were assessed based on thorax CT scanning. Patients were treated with modification of diet and proton pump inhibitors. The response to treatment was assessed by the change in quality of life (QOL) measured by Leicester Cough Questionnaire (LCQ) and cough severity was measured by 100-mm visual analogue scale. Results: 45 adults (28 female, 17 male) were included. Hiatal hernia was demonstrated in 12 (26.6%) patients. Patients with hiatal hernia did not differ from those without hiatal hernia in clinical characteristics, cough duration and severity and cough-related QOL. We found moderate positive correlations between maximal sagittal diameter of hiatal hernia and cough severity (ρ=0.692, p=0.013) and duration (ρ=0.720, p=0.008). Patients without hiatal hernia responded better to antireflux therapy, with significant LCQ improvement. A strong negative correlation between sagittal diameter of hiatal hernia gate and increase in LCQ (ρ= -0.764, p=0.004) was demonstrated. Conclusion: The presence of hiatal hernia identified in chest CT may impact cough severity, duration and response to antireflux treatment in patients with GOR-related chronic cough. Further prospective studies are justified to confirm significance of hiatal hernia in the management of chronic cough.

The impact of spontaneous cough on pleural pressure changes during therapeutic thoracentesis.

Cough during therapeutic thoracentesis (TT) is considered an adverse effect. The study was aimed to evaluate the relationship between cough during TT and pleural pressure (Ppl) changes (∆P). Instantaneous Ppl was measured after withdrawal of predetermined volumes of pleural fluid. Fluid withdrawal (FW) and Ppl measurement (PplM) periods were analyzed separately using the two sample Kolmogorov-Smirnov test and the nonparametric skew to assess differences between ∆P distributions in periods with and without cough. The study involved 59 patients, median age 66 years, median withdrawn fluid volume 1800 mL (1330 ÷ 2400 mL). In total, 1265 cough episodes were recorded in 52 patients, in 24% of FW and 19% of PplM periods, respectively. Cough was associated with significant changes in ∆P distribution (p < 0.001), decreasing the left tail of ∆P distribution for FW periods (the skew = - 0.033 vs. - 0.182) and increasing the right tail for PplM periods (the skew = 0.182 vs. 0.088). Although cough was more frequent in 46 patients with normal pleural elastance (p < 0.0001), it was associated with significantly higher ∆P in patients with elevated elastance (median Ppl increase 2.9 vs. 0.2 cmH2O, respectively). Cough during TT is associated with small but beneficial trend in Ppl changes, particularly in patients with elevated pleural elastance, and should not be considered solely as an adverse event.

Inflammatory Phenotypes of Cough Variant Asthma as Response Predictors to Anti-Asthmatic Therapy.

BACKGROUND: Eosinophilic inflammatory phenotype was thought to be the most common phenotype of cough variant asthma (CVA), nevertheless other phenotypes were also reported. PURPOSE: The study aimed to analyze the inflammatory phenotypes of CVA in relation to treatment response to the stepwise anti-asthmatic treatment. PATIENTS AND METHODS: The study included 45 patients with chronic cough (CC) and suspicion of CVA (normal chest X-ray, presence of bronchial hyperresponsiveness and no history of wheezing or dyspnea) in whom induced sputum was successfully collected. Based on the cellular composition of the sputum, patients were divided into major inflammatory phenotypes: eosinophilic, neutrophilic, paucigranulocytic or mixed granulocytic. A stepwise treatment, including inhaled corticosteroids with long-acting ß2-agonist, montelukast and short-term therapy with prednisone was initiated. Good treatment response was defined as the reduction in cough severity at least 20 mm from the baseline in visual analogue scale and improvement in cough-related quality of life assessed by the Leicester cough questionnaire at least 1.3 points after any of three steps. RESULTS: Finally, 40/45 (88.9%) patients improved after therapy. Eosinophilic asthma was found in 13/40 (32.5%) patients, neutrophilic in 6/40 (15.0%) and paucigranulocytic pattern in 21/40 (52.5%) patients. No one demonstrated a mixed granulocytic phenotype. The response to the treatment was similar in all groups. However, the reduction in cough severity was inversely related to the percentage of sputum neutrophils (r = -0.44, P = 0.003). We showed that the percentage of neutrophils in sputum >46% may be considered as a predictor of poor response to anti-asthmatic therapy. CONCLUSION: The diversity of inflammatory phenotypes with paucigranulocytic preponderance was found in subjects with CVA. The response to anti-asthmatic treatment in patients with CVA was not related to the inflammatory phenotype. High neutrophil count in sputum may predict poor response to anti-asthmatic therapy in patients with CC and bronchial hyperresponsiveness.

Impact of therapeutic thoracentesis and pleural pressure changes on breathing pattern, dyspnea, lung function, and arterial blood gases.

INTRODUCTION: Therapeutic thoracentesis is highly effective in providing symptomatic improvement in patients with large volume pleural effusion (PE). However, some physiological effects of pleural fluid (PF) withdrawal are still not fully elucidated. OBJECTIVES: The study aimed to evaluate alterations in the breathing pattern, pulmonary function, and arterial blood gases (ABG) in relation to both withdrawn PF volume and pleural pressure (Ppl) changes in patients undergoing therapeutic thoracentesis. PATIENTS AND METHODS: This prospective, observational, cross­sectional study included 37 patients with large volume PE. Respiratory rate (RR), dyspnea, pulmonary function, and ABG were assessed before the thoracentesis, at the termination of the PF withdrawal and 1, 3, and 24 hours after the procedure. The volume of PF drained, Ppl, and tidal volume (TV) were monitored during the thoracentesis. RESULTS: Thoracentesis resulted in a transient but significant increase in RR directly after the procedure, and a transient decrease, followed by subsequent increase in TV. There was a significant and constant increase in forced vital capacity up to 24 hours after thoracentesis (P = 0.001). Oxygen partial pressure (PaO2) significantly improved directly after PF withdrawal (P = 0.01) and returned to baseline values after 24 hours. Thoracentesis was invariably associated with a significant increase in the amplitude of Ppl (Ppl_ampl) changes during the respiratory cycle (P <0.001). CONCLUSIONS: Therapeutic thoracentesis results in a modest improvement in pulmonary function, tran-sient increase in PaO2 and increase in Ppl_ampl. The improvement in pulmonary function and ABG is closely related to the volume of PF drained and pleural elastance. The increase in Ppl_ampl probably represents a more efficient work of the respiratory muscles.

Tracheobronchial manifestations of Aspergillus infections.

Human lungs are constantly exposed to a large number of Aspergillus spores which are present in ambient air. These spores are usually harmless to immunocompetent subjects but can produce a symptomatic disease in patients with impaired antifungal defense. In a small percentage of patients, the trachea and bronchi may be the main or even the sole site of Aspergillus infection. The clinical entities that may develop in tracheobronchial location include saprophytic, allergic and invasive diseases. Although this review is focused on invasive Aspergillus tracheobronchial infections, some aspects of allergic and saprophytic tracheobronchial diseases are also discussed in order to present the whole spectrum of tracheobronchial aspergillosis. To be consistent with clinical practice, an approach basing on specific conditions predisposing to invasive Aspergillus tracheobronchial infections is used to present the differences in the clinical course and prognosis of these infections. Thus, invasive or potentially invasive Aspergillus airway diseases are discussed separately in three groups of patients: (1) lung transplant recipients, (2) highly immunocompromised patients with hematologic malignancies and/or patients undergoing hematopoietic stem cell transplantation, and (3) the remaining, less severely immunocompromised patients or even immunocompetent subjects.

Blood eosinophils as a predictor of treatment response in adults with difficult-to-treat chronic cough.

There is lack of evidence on the role of blood eosinophil count (BEC) as a predictor of treatment response in patients with chronic cough. The study aimed to evaluate BEC as a predictor of treatment response in all non-smoking adults with chronic cough and normal chest radiograph referred to cough clinic and in a subgroup of patients with chronic cough due to asthma or non-asthmatic eosinophilic bronchitis (NAEB). This prospective cohort study included 142 consecutive, non-smoking patients referred to our cough centre due to chronic cough. The management of chronic cough was performed according to the current recommendations. At least a 30-mm decrease of 100-mm visual analogue scale in cough severity and a 1.3 points improvement in Leicester Cough Questionnaire were classified as a good therapeutic response. There was a predominance of females (72.5%), median age 57.5 years with long-lasting, severe cough (median cough duration 60 months, severity 55/100 mm). Asthma and NAEB were diagnosed in 47.2% and 4.9% of patients, respectively. After 12-16 weeks of therapy, a good response to chronic cough treatment was found in 31.0% of all patients. A weak positive correlation was demonstrated between reduction in cough severity and BEC (r=0.28, p<0.001). Area under the curve for all patients with chronic cough was 0.62 with the optimal BEC cut-off for prediction of treatment response set at 237 cells·µL-1 and for patients with chronic cough due to asthma/NAEB was 0.68 (95% CI 0.55-0.81) with the cut-off at 150 cells·µL-1. BEC is a poor predictor of treatment response in adults with chronic cough treated in the cough centre.

Looking ahead to novel therapies for chronic cough. Part 1 - peripheral sensory nerve targeted treatments.

INTRODUCTION: Due to a relatively high prevalence and negative impact on quality of life chronic cough (CC) is a challenge for both patients and clinicians. There is ongoing research to address the unmet need and develop more effective antitussive treatment options. This is the first part of a series of two reviews of new antitussive medications. Medical databases (Medline, Embase and SCOPUS) and trial registries (ClinicalTrials.gov and EudraCT) were searched for studies on antitussive drugs targeting peripheral sensory nerves. AREAS COVERED: This review presents current knowledge of peripheral receptors that are not only involved in evoking the cough reflex, but are also potentially responsible for more sustained neural alterations. Blockage of the receptors and ion channels is discussed in terms of its potential antitussive effect. EXPERT OPINION: Although better understanding of CC mechanisms has facilitated the development of novel treatments including P2X2/3 receptor inhibitors (e.g. gefapixant), there remain several gaps in the knowledge about the mechanisms and treatment of CC. These include the lack of tests to diagnose cough hypersensitivity syndrome and predictors of response to specific treatments. Further research into cough phenotypes and endotypes will yield important insights and a personalized approach to cough management.

Pleural Pressure Pulse in Patients with Pleural Effusion: A New Phenomenon Registered during Thoracentesis with Pleural Manometry.

Pleural manometry enables the assessment of physiological abnormalities of lung mechanics associated with pleural effusion. Applying pleural manometry, we found small pleural pressure curve oscillations resembling the pulse tracing line. The aim of our study was to characterize the oscillations of pleural pressure curve (termed here as the pleural pressure pulse, PPP) and to establish their origin and potential significance. This was an observational cross-sectional study in adult patients with pleural effusion who underwent thoracentesis with pleural manometry. The pleural pressure curves recorded prior to and during fluid withdrawal were analyzed. The presence of PPP was assessed in relation to the withdrawn pleural fluid volume, lung expandability, vital and echocardiographic parameters, and pulmonary function testing. A dedicated device was developed to compare the PPP to the pulse rate. Fifty-four patients (32 women) median age 66.5 (IQR 58.5-78.7) years were included. Well visible and poorly visible pressure waves were detected in 48% and 35% of the patients, respectively. The frequency of PPP was fully concordant with the pulse rate and the peaks of the oscillations reflected the period of heart diastole. PPP was more visible in patients with a slower respiratory rate (p = 0.008), a larger amount of pleural effusion, and was associated with a better heart systolic function assessed by echocardiography (p < 0.05). This study describes a PPP, a new pleural phenomenon related to the cyclic changes in the heart chambers volume. Although the importance of PPP remains largely unknown, we hypothesize that it could be related to lung atelectasis or lower lung and visceral pleura compliance.

[Hemorrhagic parapneumonic effusion in a 64 year-old patient as the first symptom of hemophilia B]. / Krwisty wysiek parapneumoniczny jako pierwszy objaw hemofilii B u 64-letniego mezczyzny.

Hemophilia B is an inherited, X chromosome-linked disease. It is usually diagnosed in childhood, sometimes in adolescence. The commonest symptoms include spontaneous or post-traumatic bleeding into the joints and/or muscles, as well as mucosal bleeding. Respiratory symptoms are rarely reported. We present the case of a 64 year-old man in whom bloody parapneumonic effusion (hemothorax) was the first symptom of hemophilia B. The reason for prolonged activated partial thromboplastin time (APTT) found on admission has not been elucidated. Since antibiotic therapy and pleural tube thoracostomy with intrapleural streptokinase were found to be ineffective, video-assisted thoracic surgery was performed with the right lung decortication. Post-operative treatment was complicated by massive pleural bleeding requiring two subsequent thoracotomies. Additional blood tests revealed factor IX deficiency and resulted in hemophilia B being diagnosed. The presented case proves that hereditary bleeding disorders may be diagnosed even in late adulthood. Intrapleural bleeding related to pneumonia and pleural inflammation might be the first presenting symptom. Hemophilia should be considered as a potential cause of APTT prolongation, even in an elderly patient with atypical presentation. Explaining the reason for APTT prolongation before the surgical procedure could have allowed to avoid severe bleeding in the described patient.