Assessing the applicability of the new Global Lung Function Initiative reference values for the diffusing capacity of the lung for carbon monoxide in a large population set.

BACKGROUND: The single-breath diffusing capacity of the lung for carbon monoxide (DLCO) interpretation needs the comparison of measured values to reference values. In 2017, the Global Lung Function Initiative published new reference values (GLI-2017) for DLCO, alveolar volume (VA) and transfer coefficient of the lung for carbon monoxide (KCO). We aimed to assess the applicability of GLI-2017 reference values for DLCO on a large population by comparing them to the European Community of Steel and Coal equations of 1993 (ECSC-93) widely used. METHODS: In this retrospective study, spirometric indices, total lung capacity, DLCO, VA and KCO were measured in adults classified in 5 groups (controls, asthma, chronic bronchitis, cystic fibrosis, and interstitial lung diseases (ILD)). Statistical analysis comparing the 2 equations sets were stratified by sex. RESULTS: 4180 tests were included. GLI-2017 z-scores of the 3 DLCO indices of the controls (n = 150) are nearer to 0 (expected value in a normal population) than ECSC-93 z-scores. All groups combined, in both genders, DLCO GLI-2017 z-scores and %predicted are significantly higher than ECSC z-scores and %predicted. In the ILD group, differences between the 2 equation sets depend on the DLCO impairment severity: GLI-2017 z-scores are higher than ECSC z-scores in patients with no or "mild" decrease in DLCO, but are lower in "moderate" or "severe" decrease. CONCLUSION: GLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases.

Establishment of a mouse model with all four clinical features of eosinophilic bronchitis.

Eosinophilic bronchitis (EB) is a clinical disease characterized by chronic cough, airway eosinophil infiltration, and responsive to steroid therapy but with the absence of airway hyperreactivity (AHR). This study established an EB mouse model with all the above features. First, 42 mice were divided into 7 groups to investigate the optimal time interval between cough and AHR detections. Afterward, 28 mice were divided into the asthma, EB, normal saline (NS), and dexamethasone (DXM) groups. Mice were challenged using nasal drops of 200 µg ovalbumin (OVA), 10 µg OVA, NS, or intraperitoneal injections of 5 mg/kg of DXM one hour prior to 10 µg OVA challenge. Airway reactivity was measured 6 h after cough was observed. The frequency of coughs in the asthma and EB groups increased significantly compared to mice in the NS group. After DXM administration, frequency of coughs was significantly decreased compared to mice in the asthma and EB groups. Lung resistance in the asthma group was significantly higher compared to mice in the NS, EB, and DXM groups. Obvious airway eosinophilic inflammation in BALF and lung tissues were observed in the asthma and EB groups, while DXM administration could attenuate airway inflammatory infiltration. In summary, we developed a mouse EB model with all four clinical features of EB by the administration of 10 µg OVA nasal drops.

Quantitative Assessment of Regional Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study investigates the value of regional clearance measurements in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (i) healthy nonsmoking controls (NSCs) (n = 9), (ii) smoking controls (SCs) who were current smokers with normal lung function (n = 10), and (iii) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volumes at 1 second (FEV1) for the three groups were 109 (± 18), 94 (± 5), and 78 (± 12), respectively. After inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Both lung clearance and tracheobronchial clearance (TBC) (normalized to 24 hours clearance) were calculated for inner and outer lung zones. Inner zone clearance was corrected for input from the outer zone. A novel parameter, the bronchial airways clearance index (BACI), which combined clearance data from both zones, was also evaluated. Regional results were compared with whole lung clearance in the same subjects. Results: Corrected inner zone clearance at 3 hours was not reduced compared with NSC in either SCs or COPD. Outer zone clearance was higher in COPD than in the other groups. Corrected inner zone TBC showed significant reductions in SC and COPD compared with NSC. BACI was significantly reduced in COPD compared with NSC and also correlated with FEV1. The mean BACI for SC was also reduced compared with NSC, but the distribution of results was bimodal, with a significant proportion of subjects having values in the NSC range. Conclusions: Regional MCC demonstrated differences between NSCs, SCs, and subjects with mild-to-moderate COPD, which were not apparent with whole lung measurements.

Tidal breathing flow profiles during sleep in wheezing children measured by impedance pneumography.

For the first time, impedance pneumography (IP) enables a continuous analysis of the tidal breathing flow volume (TBFV), overnight. We studied how corticosteroid inhalation treatments, sleep stage, and time from sleep onset modify the nocturnal TBFV profiles of children. Seventy children, 1-5 years old and with recurrent wheezing, underwent three, full-night TBFVs recordings at home, using IP. The first recorded one week before ending a 3-months inhaled corticosteroids treatment, and remaining two, 2 and 4 weeks after treatment. TBFV profiles were grouped by hour from sleep onset and estimated sleep stage. Compared with on-medication, the off-medication profiles showed lower volume at exhalation peak flow, earlier interruption of expiration, and less convex middle expiration. The differences in the first two features were significant during non-rapid eye movement (NREM), and the differences in the third were more prominent during REM after 4 h of sleep. These combinations of TBFV features, sleep phase, and sleep time potentially indicate airflow limitation in young children.

Decompression of the thoracic duct: A novel transcatheter approach.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

Response to bronchodilator and clinical, pathophysiological features in patients with nonasthmatic eosinophilic bronchitis.

INTRODUCTION: Whether nonasthmatic eosinophilic bronchitis (NAEB) shows response to bronchodilator (RB) remains unclear. OBJECTIVES: To investigate the RB and its relationship with clinical and pathophysiological features in NAEB. METHODS: Fifty-one patients with NAEB were assigned in a 2:1 ratio to receive oral bambuterol hydrochloride (n = 34, 10 mg, once daily, for 3 days) or matched placebo (n = 17) randomly, of whom 48 patients (32 with bronchodilator and 16 with placebo) completed the study. Sputum induction, spirometry and cough reflex sensitivity were measured. RB was considered when cough Visual analogue scale (VAS) score decreased 30% or more after treatment. Cough reflex sensitivity was defined as the lowest concentration of capsaicin inducing five coughings or more (C5), and presented as Log C5. RESULTS: The responsive rate of patients with bronchodilator was significantly higher than that with placebo (34.4% vs 6.3%, P < 0.05). The VAS score decreased significantly in patients with bronchodilator (median: 6.0-3.0, P < 0.01). There was a significantly higher median Log C5 (2.7 vs 1.3, P < 0.05), and a higher trend of decline in FEV1 % predicted and MMEF% predicted after bronchial provocation in patients with RB as compared with patients without RB. No significant differences in baseline percentages of sputum eosinophil were found between patients with RB and that without RB. CONCLUSIONS: One third of patients with NAEB respond well to bronchodilator treatment, which are related with lower cough reflex sensitivity and increased airway responsiveness. The relationship between NAEB and asthma needs to be investigated further.

Time course of nocturnal cough and wheezing in children with acute bronchitis monitored by lung sound analysis.

Cough and wheezing are the predominant symptoms of acute bronchitis. Hitherto, the evaluation of respiratory symptoms was limited to subjective methods such as questionnaires. The main objective of this study was to objectively determine the time course of cough and wheezing in children with acute bronchitis. The impact of nocturnal cough on parent's quality of life was assessed as secondary outcome. In 36 children (2-8 years), the frequency of nocturnal cough and wheezing was recorded during three nights by automated lung sound monitoring. Additionally, parents completed symptom logs, i.e., the Bronchitis Severity Score (BSS), as well as the Parent-proxy Children's Acute Cough-specific Quality of Life Questionnaire (PAC-QoL). During the first night, patients had 34.4 ± 52.3 (mean ± SD) cough epochs, which were significantly reduced in night 5 (13.5 ± 26.5; p < 0.001) and night 9 (12.8 ± 28.1; p < 0.001). Twenty-two patients had concomitant wheezing, which declined within the observation period as well. All subjective parameters (BSS, Cough log and PAC-QoL) were found to be significantly correlated with the objectively assessed cough parameters.Conclusion: Long-term recording of cough and wheezing offers a useful opportunity to objectively evaluate the time course of respiratory symptoms in children with acute bronchitis. To assess putative effects of pharmacotherapy on nocturnal bronchitis symptoms, future studies in more homogeneous patient groups are needed. What is Known: • Cough and wheezing are the predominant symptoms of acute bronchitis. • There is a diagnostic gap in long-term assessment of these respiratory symptoms, which needs to be closed to optimize individual therapies. What is New: • Long-term recording of nocturnal cough and wheezing allows for objective evaluation of respiratory symptoms in children with acute bronchitis and provides a tool to validate the efficacy of symptomatic bronchitis therapies.

Predictors of Adverse Outcomes in Uncomplicated Lower Respiratory Tract Infections.

PURPOSE: Presentation with acute lower respiratory tract infection (LRTI) in primary care is common. The aim of this study was to help clinicians treat patients presenting with LRTI in primary care by identifying those at risk of serious adverse outcomes (death, admission, late-onset pneumonia). METHODS: In a prospective cohort study of patients presenting with LRTI symptoms, patient characteristics and clinical findings were recorded and adverse events identified over 30 days by chart review. Multivariable logistic regression analyses identified predictors of adverse outcomes. RESULTS: Participants were recruited from 522 UK practices in 2009-2013. The analysis was restricted to the 28,846 adult patients not referred immediately to the hospital. Serious adverse outcomes occurred in 325/28,846 (1.1%). Eight factors were independently predictive; these characterized symptom severity (absence of coryza, fever, chest pain, and clinician-assessed severity), patient vulnerability (age >65 years, comorbidity), and physiological impact (oxygen saturation <95%, low blood pressure). In aggregate, the 8 features had moderate predictive value (area under the receiver operating characteristic curve 0.71, 95% CI, 0.68-0.74); the 4% of patients with ≥5 features had an approximately 1 in 17 (5.7%) risk of serious adverse outcomes, the 35% with 3 or 4 features had an intermediate risk (1 in 50, 2.0%), and the 61% with ≤2 features had a low (1 in 200, 0.5%) risk. CONCLUSIONS: In routine practice most patients presenting with LRTI in primary care can be identified as at intermediate or low risk of serious outcome.

Surface-enhanced raman spectroscopy: A non invasive alternative procedure for early detection in childhood asthma biomarkers in saliva.

The early detection of bronchial inflammation in asthma, through a non-invasive, simple method and under a subclinical state, could lead to a more effective control of this condition. The aim of this study was to identify biomarkers of bronchial inflammation in the saliva of children with asthma through immunoassay and Surface Enhanced Raman Spectroscopy (SERS). We conducted an analytical cross-sectional study in 44 children ages 6-12; the diagnosis of asthma was made according to Global Initiative for Asthma (GINA) standards. The children's saliva was analyzed by immunoassay for the quantification of 37 cytokines, as well as SERS analysis in a confocal Raman microscope at 785 nm. We found a significant association between bronchial obstruction and IL-8 (p = 0.004), IL-10 (p = 0.008) and sCD163 (p = 0.003). The Raman spectra showed significant amplification in the region of 760 to 1750 cm-1. The Principal Component Analysis and Linear Discriminant Analysis (PCA-LDA) method has a sensitivity of 85%, specificity of 82% and an accuracy of 84% for the diagnosis of asthma. These results demonstrate the presence of a subclinical inflammatory state, suggestive of bronchial remodeling in the population studied. The SERS method is a potential tool for identifying bronchial inflammation and its endotype, allowing for a highly sensitive and specific diagnosis.

Why chronic cough in children is different.

Recently, there have been robust changes in our knowledge of the neurophysiology of cough and novel clinical etiologies. Specifically, cough hypersensitivity in adults and protracted bacterial bronchitis (PBB) in children have been increasingly investigated, and differences between chronic cough in children and adults have been widely reported. In young children, postinfectious cough, bronchiectasis, airway malacia, PBB, and asthma appear to be the main causes of cough; however, by adolescence, the causes of cough are more likely to become those common in adults, namely, gastroesophageal reflux, asthma, and upper airway syndrome. These differences are attributed to changes in various characteristics of the respiratory tract, immune system, and nervous system between children and adults. New knowledge about the neural aspects of cough has revealed a complex network of pathways that initiate cough. The effect of inflammation on cough neural processing occurs at multiple peripheral and central sites within the nervous system. Evidence exists that direct or indirect neuroimmune interaction induces a complex response, which can be altered by mediators released by the sensory or parasympathetic neurons and vice versa. During childhood, the respiratory tract and the nervous system undergo a series of anatomical and physiological maturation processes that produce the cough neural circuits. Alterations provoked by various pathological processes, noxious agents, infection, and inflammation during the developmental period can lead to persistent or irreversible modifications, which may explain why many adult patients, in addition to expressing high cough sensitivity, remain refractive to disease-specific therapies.

Colistin Use in Patients with Chronic Kidney Disease: Are We Underdosing Patients?

Colistin is administered as its inactive prodrug colistimethate (CMS). Selection of an individualized CMS dose for each patient is difficult due to its narrow therapeutic window, especially in patients with chronic kidney disease (CKD). Our aim was to analyze CMS use in patients with CKD. Secondary objectives were to assess the safety and efficacy of CMS in this special population. In this prospective observational cohort study of CMS-treated CKD patients, CKD was defined as the presence of a glomerular filtration rate (GFR) < 60 mL/min/m² for more than 3 months. The administered doses of CMS were compared with those recently published in the literature. Worsened CKD at the end of treatment (EOT) was evaluated with the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. Colistin plasma concentrations (Css) were measured using high-performance liquid chromatography. Fifty-nine patients were included. Thirty-six (61.2%) were male. The median age was 76 (45⁻95) years and baseline GFR was 36.6 ± 13.6. The daily mean CMS dosage used was compared with recently recommended doses (3.36 vs. 6.07; p < 0.001). Mean Css was 0.9 (0.2⁻2.9) mg/L, and Css was <2 mg/L in 50 patients (83.3%). Clinical cure was achieved in 43 (72.9%) patients. Worsened renal function at EOT was present in 20 (33.9%) patients and was reversible in 10 (52.6%). The CMS dosages used in this cohort were almost half those currently recommended. The mean achieved Css were under the recommended target of 2 mg/dL. Despite this, clinical cure rate was high. In this patient cohort, the incidence of nephrotoxicity was similar to those found in other recent studies performed in the general population and was reversible in 52.6%. These results suggest that CMS is safe and effective in patients with CKD and may encourage physicians to adjust dosage regimens to recent recommendations in order to optimize CMS treatments.

Increased Sputum IL-17A Level in Non-asthmatic Eosinophilic Bronchitis.

BACKGROUND: Non-asthmatic eosinophilic bronchitis (NAEB) is one common cause of chronic cough which is characterized as airway eosinophilic inflammation like asthma but lack of airway hyper-responsiveness. Previous studies showed that Th2-pathway plays a role in NAEB, but the role of non-Th2 pathway in mechanism of NAEB remains unknown. Recently, IL-17A, a Th17-pathway cytokine, has been demonstrated to be involved in asthma development. However, the relationship between Th17-pathway and NAEB is unknown. METHODS: We aim to assess the airway level of IL-17A in the subjects with NAEB. Relationships between the IL-17A level and airway function in NAEB or asthma are also observed. We measured IL-17A concentrations in the sputum supernatant from 12 subjects with EB, 16 subjects with asthma [9 eosinophilic asthmatic (EA) and 7 non-eosinophilic asthmatic (NEA) according to the sputum eosinophil ≥ 3%], and 9 healthy control subjects. RESULTS: Increasing IL-17A level was found in NAEB group (29.65 ± 8.13 pg/ml), EA group (32.45 ± 3.22 pg/ml), and NEA group (29.62 ± 6.91 pg/ml) compared with the healthy control group (17.05 ± 10.30 pg/ml) (P < 0.05, P < 0.01, P < 0.05, respectively). The sputum IL-17A level was correlated with FENO (r = 0.44, P < 0.01), FEV1/FVC% (r = - 0.38, P < 0.05), MMEF%pred (r = - 0.34, P < 0.05), and sputum neutrophil% (r = 0.33, P < 0.05) in total. CONCLUSION: Th17-pathway may play a role not only in asthmatics, but also in subjects with NAEB, as reflected by increasing IL-17A concentrations in sputum supernatant.

Evaluation of an incidental cardiac finding in a patient with bronchitis.

CLINICAL INTRODUCTION: A 63-year-old man with HIV presented with 1 month of dyspnoea and productive cough without orthopnoea. He was afebrile with normal blood pressure, borderline tachycardia and mild pulmonary wheezing. He had exertional hypoxia requiring 4 L per minute of oxygen. No murmurs, jugular venous distention or lower extremity oedema was noted. Clinical evaluation included transthoracic echocardiography (TTE), which showed mild left ventricular hypertrophy with normal size and systolic function. The right ventricle was normal. There was mild aortic insufficiency; other valves were normal. An abnormality was incidentally seen at the aortic root.The patient was treated for bronchitis and chronic obstructive pulmonary disease exacerbation, while further evaluation of the incidental aortic root finding was performed with transoesophageal echocardiography (TEE) and cardiac MRI (CMR). QUESTION: What is the most likely diagnosis for this finding?Sinus of Valsalva aneurysm.Chronic aortic dissection.Left ventricular outflow tract (LVOT) pseudoaneurysm.Right coronary artery aneurysm.Aortic root abscess.

Successful Treatment of Protein-Losing Enteropathy and Plastic Bronchitis by Biphasic Cuirass Ventilation in a Patient with Failing Fontan Circulation.

We present a 16-year-old male patient with hypoplastic left heart syndrome who developed protein-losing enteropathy (PLE) and plastic bronchitis (PB) after a Fontan operation. He received medical therapies, including albumin infusion, unfractionated heparin, and high-dose anti-aldosterone therapy but could not obtain clinical relief. Biphasic cuirass ventilation (BCV) led to expectoration of bronchial casts and prompt resolution of PB. Notably, clinical symptoms related to PLE were dramatically improved after starting BCV. A brief period of BCV increased stroke volume from 26±1.4 to 39±4.0 mL. This case suggests that BCV could be an effective treatment for PLE in patients with failing Fontan circulation.

Gastroesophageal reflux symptoms and nasal symptoms affect the severity of bronchitis symptoms in patients with chronic obstructive pulmonary disease.

BACKGROUND: Cough and sputum production (symptoms of bronchitis) are common in chronic obstructive pulmonary disease (COPD). Extrapulmonary comorbidities, such as gastroesophageal reflux disease (GERD) and post-nasal drip, also cause bronchitis symptoms. The impact of extrapulmonary comorbidities on the severity of bronchitis symptoms in COPD is unknown. The aim of this study was to quantify bronchitis symptoms and assess the impact of GERD and nasal symptoms on the severity of bronchitis symptoms in COPD. METHODS: In this cross-sectional study, stable COPD patients were recruited and completed the COPD assessment test (CAT) and Cough and Sputum Assessment Questionnaire (CASA-Q) to quantify bronchitis symptoms. To evaluate extrapulmonary comorbidities, the Frequency Scale for Symptoms of GERD (FSSG) questionnaire and nasal symptom questionnaire were completed. The impact of these comorbidities on the severity of bronchitis symptoms was analyzed. RESULTS: Ninety-nine COPD patients were recruited. The presence of GERD symptoms (24.2% in the study population) was associated with more sputum symptoms. The presence of nasal discharge (43.4%) was associated with more cough and sputum symptoms, whereas post-nasal drip (13.1%) was associated with more sputum symptoms. On multivariate analyses, nasal discharge was associated with more cough symptoms. GERD and post-nasal drip were associated with more sputum symptoms. CONCLUSION: This study showed that the presence of GERD and/or nasal symptoms is associated with an increase in bronchitis symptoms. Careful assessment of extrapulmonary comorbidities is necessary in the evaluation of bronchitis symptoms in COPD patients.

Bronchiectasis, Chronic Suppurative Lung Disease and Protracted Bacterial Bronchitis.

Bronchiectasis is a structural airway disease characterized by dilated bronchi and bronchioles due to severe or recurrent lower airways inflammation. Bronchiectasis can occur as a result of chronic pulmonary aspiration. Bronchiectasis may also be associated with a wide variety of systemic diseases, which should be considered in the differential diagnosis. Children with bronchiectasis typically have a chronic or recurrent productive cough and carry a significant burden of disease with a considerable impact on quality of life. The diagnosis of bronchiectasis is made by high-resolution chest computerized tomography. Aggressive management of bronchiectasis is necessary to reduce the daily symptom burden and frequency of exacerbations. Chronic suppurative lung disease may be a precursor to bronchiectasis, only lacking the defining radiographic features of bronchiectasis. Children with chronic suppurative lung disease may have the same symptoms as children with bronchiectasis and should be treated similarly. Protracted bacterial bronchitis is defined as a cough lasting at least four weeks that responds to antibiotic therapy. Protracted bacterial bronchitis may occur following a viral respiratory tract infection. Protracted bacterial bronchitis can be treated with a prolonged course of empiric antibiotics. Further evaluation is necessary if a child with suspected protracted bacterial bronchitis does not adequately respond to antibiotics as chronic suppurative lung disease or bronchiectasis must be considered.