Application of Precise Positioning for Sputum Expectoration in ICU Patients with Pulmonary Infection.

OBJECTIVE: To determine the application value of precise positioning for sputum expectoration in intensive care unit (ICU) hospitalized patients with pulmonary infection (PI). METHODS: A total of 183 patients with PI treated in the ICUs of Shengjing Hospital of China Medical University from June 2019 to June 2020 were divided into a control group (n = 91) and an observation group (n = 92), all of whom received conventional drug therapy. The control group was given routine nursing intervention, based on which, the observation group was supplemented with precise positioning for sputum expectoration. The 24-hour sputum volume, respiratory rate (RR), blood gas analysis indexes, inflammatory indicators, Clinical Pulmonary Infection Score (CPIS), Modified Medical Research Council (mMRC) dyspnea scale score, and quality of life (36-Item Short-Form Health Survey, SF-36) were observed in both arms before and after intervention. The incidence of adverse reactions was counted. RESULTS: The observation group showed better mMRC scores than the control group (P < 0.05). Compared with the control group, the sputum volume, RR, and CPIS score were lower, and the SF-36 score was higher in the observation group 7 days after intervention (P < 0.05). After intervention, the oxygen saturation (SaO2) and partial pressure of oxygen (PaO2) were higher, while the carbon dioxide partial pressure (PaCO2), C-reactive protein (CRP), procalcitonin (PCT), and leukocyte count were lower in the observation group compared with the control group (P < 0.05). There was no significant difference in the incidence of complications between the two arms (P > 0.05). CONCLUSION: The application of precise positioning for sputum expectoration in nursing intervention of ICU patients with PI can alleviate the severity of PI and dyspnea, reduce inflammatory reaction, and improve the quality of life of patients.

Tiotropium Bromide Attenuates Mucus Hypersecretion in Patients with Stable Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with stable chronic obstructive pulmonary disease (COPD) have been observed to benefit from tiotropium bromide. However, there are few studies of tiotropium bromide on sputum and sputum viscosity. To evaluate the effect of tiotropium bromide on mucus hypersecretion, a randomized, double-blind controlled trial was performed. METHODS: 120 cases of patients with pulmonary function grade II were divided into two groups, which include the treatment group given tiotropium bromide powder inhalation (18 µg, inhalation, QD) and the control group given formoterol fumarate powder inhalation (12 µg, inhalation, BID) plus ambroxol hydrochloride tablets (60 mg, oral, TID). After 3 months of treatment, the pulmonary function and α 1-acid glycoprotein (α 1-AGP) in sputum were detected, and the changes of glycoprotein and Ca2+ content were evaluated by Miller classification. RESULTS: Three patients (2 cases in the treatment group and 1 case in the control group) were dropped due to loss of follow-up, and 117 cases of patients were enrolled in this study. After 3 months of treatment, the sputum character score, α1-acid glycoprotein, Ca2+ content, and lung function of the two groups were significantly improved; group comparison analyses revealed that there was no significant difference in the content of α 1-AGP, Ca2+ in sputum, and lung function between the two groups (P > 0.05), but the improvement of sputum properties was significant (P < 0.05), and the treatment group was better than the control group (t = -2.77; P = 0.007). CONCLUSIONS: Inhaled tiotropium bromide can effectively inhibit the mucus hypersecretion in stable COPD patients, improve the sputum properties and lung function of patients, and improve the quality of life of patients.

Rheological effects of hypertonic saline and sodium bicarbonate solutions on cystic fibrosis sputum in vitro.

BACKGROUND: Cystic fibrosis (CF) is a life-threatening multiorgan genetic disease, particularly affecting the lungs, where recurrent infections are the main cause of reduced life expectancy. In CF, mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein impair transepithelial electrolyte and water transport, resulting in airway dehydration, and a thickening of the mucus associated with abnormal viscoelastic properties. Our aim was to develop a rheological method to assess the effects of hypertonic saline (NaCl) and NaHCO3 on CF sputum viscoelasticity in vitro, and to identify the critical steps in sample preparation and in the rheological measurements. METHODS: Sputum samples were mixed with hypertonic salt solutions in vitro in a ratio of either 10:4 or 10:1. Distilled water was applied as a reference treatment. The rheological properties of sputum from CF patients, and the effects of these in vitro treatments, were studied with a rheometer at constant frequency and strain, followed by frequency sweep tests, where storage modulus (G'), loss modulus (G″) and loss factor were determined. RESULTS: We identified three distinct categories of sputum: (i) highly elastic (G' > 100,000 Pa), (ii) elastic (100,000 Pa > G' > 1000 Pa), and (iii) viscoelastic (G' < 1000). At the higher additive ratio (10:4), all of the added solutions were found to significantly reduce the gel strength of the sputum, but the most pronounced changes were observed with NaHCO3 (p < 0.001). Samples with high elasticity exhibited the greatest changes while, for less elastic samples, a weakening of the gel structure was observed when they were treated with water or NaHCO3, but not with NaCl. For the viscoelastic samples, the additives did not cause significant changes in the parameters. When the lower additive ratio (10:1) was used, the mean values of the rheological parameters usually decreased, but the changes were not statistically significant. CONCLUSION: Based on the rheological properties of the initial sputum samples, we can predict with some confidence the treatment efficacy of each of the alternative additives. The marked differences between the three categories suggest that it is advisable to evaluate each sample individually using a rheological approach such as that described here.

Gastroesophageal reflux disease is a risk factor for sputum production in the general population: the Nagahama study.

BACKGROUND: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. METHODS: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. RESULTS: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. CONCLUSIONS: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.

Ventilator hyperinflation determined by peak airway pressure delivered: A randomized crossover trial.

AIM: The aim of this study was to see if a more sophisticated ventilator hyperinflation protocol might result in more sputum clearance compared to manual hyperinflation. BACKGROUND: Hyperinflation has been used to mobilize lung secretions in mechanically ventilated patients in the intensive care unit setting for almost 50 years. In the past decade, rather than using a bag external to the ventilator circuit to deliver hyperinflation (known as "bagging" or "manual hyperinflation"), a new technique has evolved using existing ventilator circuitry (known as "ventilator hyperinflation"). One conservative ventilator hyperinflation protocol has demonstrated equivalence with manual hyperinflation in sputum clearance. DESIGN: A randomized crossover study. METHOD: Patients received manual hyperinflation and ventilator hyperinflation in two randomly ordered treatments on the same day by the same physiotherapist, using a ventilator hyperinflation protocol involving titration of hyperinflation according to airway pressure. RESULTS: Between 2013 and 2018, 48 patients were enrolled in the study. Physiotherapy treatment using ventilator hyperinflation yielded significantly more wet weight sputum (median 2.84 g, IQR 1.81, 4.22) than treatment using manual hyperinflation (median 1.5 g, IQR 0.73, 2.31, P < .001), without significant differences in secondary measures. CONCLUSIONS: A more sophisticated approach to the titration of the volume delivered using ventilator hyperinflation relative to the airway pressure resulted in greater wet weight sputum cleared during physiotherapy treatment. RELEVANCE TO CLINICAL PRACTICE: The results presented in this paper demonstrate that the application of ventilator hyperinflation using peak airway pressure rather than tidal volume may be superior in facilitating sputum clearance and improved oxygenation without patient harm.

Exploration of the sputum methylome and omics deconvolution by quadratic programming in molecular profiling of asthma and COPD: the road to sputum omics 2.0.

BACKGROUND: To date, most studies involving high-throughput analyses of sputum in asthma and COPD have focused on identifying transcriptomic signatures of disease. No whole-genome methylation analysis of sputum cells has been performed yet. In this context, the highly variable cellular composition of sputum has potential to confound the molecular analyses. METHODS: Whole-genome transcription (Agilent Human 4 × 44 k array) and methylation (Illumina 450 k BeadChip) analyses were performed on sputum samples of 9 asthmatics, 10 healthy and 10 COPD subjects. RNA integrity was checked by capillary electrophoresis and used to correct in silico for bias conferred by RNA degradation during biobank sample storage. Estimates of cell type-specific molecular profiles were derived via regression by quadratic programming based on sputum differential cell counts. All analyses were conducted using the open-source R/Bioconductor software framework. RESULTS: A linear regression step was found to perform well in removing RNA degradation-related bias among the main principal components of the gene expression data, increasing the number of genes detectable as differentially expressed in asthma and COPD sputa (compared to controls). We observed a strong influence of the cellular composition on the results of mixed-cell sputum analyses. Exemplarily, upregulated genes derived from mixed-cell data in asthma were dominated by genes predominantly expressed in eosinophils after deconvolution. The deconvolution, however, allowed to perform differential expression and methylation analyses on the level of individual cell types and, though we only analyzed a limited number of biological replicates, was found to provide good estimates compared to previously published data about gene expression in lung eosinophils in asthma. Analysis of the sputum methylome indicated presence of differential methylation in genomic regions of interest, e.g. mapping to a number of human leukocyte antigen (HLA) genes related to both major histocompatibility complex (MHC) class I and II molecules in asthma and COPD macrophages. Furthermore, we found the SMAD3 (SMAD family member 3) gene, among others, to lie within differentially methylated regions which has been previously reported in the context of asthma. CONCLUSIONS: In this methodology-oriented study, we show that methylation profiling can be easily integrated into sputum analysis workflows and exhibits a strong potential to contribute to the profiling and understanding of pulmonary inflammation. Wherever RNA degradation is of concern, in silico correction can be effective in improving both sensitivity and specificity of downstream analyses. We suggest that deconvolution methods should be integrated in sputum omics analysis workflows whenever possible in order to facilitate the unbiased discovery and interpretation of molecular patterns of inflammation.

Clinical Role of the Chronic Obstructive Pulmonary Disease Assessment Test in Prediction of the Response to Treatment for Exacerbations.

BACKGROUND: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is a validated, eight-item questionnaire used to quantify the health status of patients. The aim of this study was to evaluate the usefulness of the CAT questionnaire as a tool to assess the response to treatment in acute exacerbations of COPD in an outpatient setting. METHODS: A multicenter, phase 3 randomized controlled trial was conducted previously to examine the efficacy and safety of oral zabofloxacin for the treatment of COPD exacerbations. In the present post hoc analysis of the original study, patients with COPD exacerbation were categorized as responders or non-responders according to the respiratory symptoms persisting on day 10 (visit 3) of treatment. The CAT questionnaire was completed daily by patients at home from the initial visit to the second visit on day 5. Subsequently, the questionnaire was completed in the presence of a physician on days 10 (visit 3) and 36 (visit 4). Multivariate regression analysis was performed to determine the association between CAT scores and the therapeutic response. RESULTS: The CAT scores decreased more rapidly in responders compared to non-responders during the first 5 days (23.3-20.4 vs. 23.5-22). Among responders, patients with higher severity of illness also revealed higher CAT scores on the first day of an exacerbation (mild, 19.8; moderate, 21.4; severe, 23.8; very severe, 28.6). Multivariate analysis revealed that a change in the CAT score during the first 3 days influenced the therapeutic response. A significant decrease in scores in the domains of sputum production, chest tightness, and activities of daily living was seen among responders. CONCLUSION: Early improvement in CAT scores may be associated with a more favorable response to the treatment of COPD exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01658020. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000532.

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

BACKGROUND: Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD). METHODS: We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients. RESULTS: Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers. Multivariate modeling on sputum microbiome, host transcriptome and proteome profiles revealed that significant associations between Moraxella and Haemophilus, host interferon and pro-inflammatory signaling pathways and neutrophilic inflammation predominated among airway host-microbiome interactions in COPD. While neutrophilia was positively correlated with Haemophilus, interferon signaling was more strongly linked to Moraxella. Moreover, while Haemophilus was significantly associated with host factors both in stable state and during exacerbations, Moraxella-associated host responses were primarily related to exacerbations. CONCLUSIONS: Our study highlights a significant airway host-microbiome interplay associated with COPD inflammation and exacerbations. These findings indicate that Haemophilus and Moraxella influence different components of host immune response in COPD, and that novel therapeutic strategies should consider targeting these bacteria and their associated host pathways in COPD.

Chronic obstructive pulmonary disease upper airway microbiota alpha diversity is associated with exacerbation phenotype: a case-control observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) frequent exacerbators (FE) suffer increased morbidity and mortality compared to infrequent exacerbators (IE). The association between the oral and sputum microbiota and exacerbation phenotype is not well defined. The objective of this study was to determine key features that differentiate the oral and sputum microbiota of FEs from the microbiota of IEs during periods of clinical stability. METHODS: We recruited 11 FE and 11 IE who had not used antibiotics or systemic corticosteroids in the last 1 month. Subjects provided oral wash and sputum samples, which underwent 16S V4 MiSeq sequencing and qPCR of 16S rRNA. Data were analyzed using Dada2 and R. RESULTS: FE and IE were similar in terms of age, FEV1 percent predicted (FEV1pp), pack-years of tobacco exposure, and St. George's Respiratory Questionnaire score. 16S copy numbers were significantly greater in sputum vs. oral wash (p = 0.01), but phenotype was not associated with copy number. Shannon diversity was significantly greater in oral samples compared to sputum (p = 0.001), and IE samples were more diverse than FE samples (p < 0.001). Sputum samples from FE had more Haemophilus and Moraxella compared to IE sputum samples, due to dominance of these COPD-associated taxa in three FE sputum samples. Amplicon sequencing variant (ASV)-level analysis of sputum samples revealed one ASV (Actinomyces) was significantly more abundant in IE vs. FE sputum (padj = 0.048, Wilcoxon rank-sum test), and this persisted after controlling for FEV1pp. Principal coordinate analysis using Bray-Curtis distance with PERMANOVA analyses demonstrated clustering by anatomic site, phenotype, inhaled corticosteroid use, current tobacco use, COPD severity, and last professional dental cleaning. CONCLUSIONS: FE have less diverse oral and sputum microbiota than IE. Actinomyces was significantly more abundant in IE sputum than FE sputum. The oral and sputum microbiota of COPD subjects cluster based on multiple clinical factors, including exacerbation phenotype. Even during periods of clinical stability, the frequent exacerbator phenotype is associated with decreased alpha diversity, beta-diversity clustering, and changes in taxonomic abundance.

Mucoid Pseudomonas aeruginosa alters sputum viscoelasticity in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION AND AIM: Pseudomonas aeruginosa could acquire a mucoid phenotype due to mutations in mucA (mucoid Pseudomonas aeruginosa - mPA) that is a hallmark of poor prognosis in patients with bronchiectasis. Despite the higher prevalence of Pseudomonas aeruginosa in bronchiectasis, how mPA and non-mucoid Pseudomonas aeruginosa (non-mPA) phenotypes could affect viscoelastic properties of sputum is unknown. Our aim was to determine the relationship between Pseudomonas aeruginosa phenotypes isolation, the viscoelastic properties of sputum and the clinical outcomes in patients with bronchiectasis. METHODS: A cross-sectional study was conducted of sputum samples obtained by spontaneous expectoration and sent for microbiology and rheology analysis. Elasticity and viscosity were measured at two oscillatory frequencies (1 and 100 rad/s). Socio-demographic and clinical data were recorded. RESULTS: We analyzed 17 patients with mPA, 14 with non-mPA and 17 with no organism reported (NOR). Compared with the NOR group, the mPA group showed higher elasticity (median 10.30 vs. 5.70, p = 0.023), viscosity (2.40 vs. 1.50, p = 0.039), and stiffness (10.70 vs. 6.00, p = 0.024). Values in the mPA group tended to be higher compared with non-mPA. Clinically, the mPA group showed greater hospitalizations during the previous year and greater affected lobes than the non-mPA and NOR groups. CONCLUSIONS: The mPA phenotype is associated with increased elasticity, viscosity and stiffness of bronchiectatic sputum. Viscoelastic properties could be used as a marker of poor mucociliary clearance in mPA, with potentially important clinical implications.

Classification of Sputum Sounds Using Artificial Neural Network and Wavelet Transform.

Sputum sounds are biological signals used to evaluate the condition of sputum deposition in a respiratory system. To improve the efficiency of intensive care unit (ICU) staff and achieve timely clearance of secretion in patients with mechanical ventilation, we propose a method consisting of feature extraction of sputum sound signals using the wavelet transform and classification of sputum existence using artificial neural network (ANN). Sputum sound signals were decomposed into the frequency subbands using the wavelet transform. A set of features was extracted from the subbands to represent the distribution of wavelet coefficients. An ANN system, trained using the Back Propagation (BP) algorithm, was implemented to recognize the existence of sputum sounds. The maximum precision rate of automatic recognition in texture of signals was as high as 84.53%. This study can be referred to as the optimization of performance and design in the automatic technology for sputum detection using sputum sound signals.

The many ways sputum flows - Dealing with high within-subject variability in cystic fibrosis sputum rheology.

We evaluated test-retest reliability of sputum viscoelastic properties in clinically stable patients with cystic fibrosis (CF). Data from a prospective, randomized crossover study was used to determine within-subject variability of sputum viscoelasticity (G', storage modulus and G", loss modulus at 1 and 10 rad s-1) and solids content over three consecutive visits. Precision of sputum properties was quantified by within-subject standard deviation (SDws), coefficient of variation (CV) and intraclass correlation coefficients (ICC). Fifteen clinically stable adults with CF (FEV1 range 24-94% predicted) were included. No differences between study visits (mean ±â€¯SD 8 ±â€¯2 days) were observed for any sputum rheology measure. CV's for G', G" and solids content ranged between 40.3-45.3% and ICC's between 0.21-0.42 indicating poor to fair test-retest reliability. Short-term within-subject variability of sputum properties is high in clinically stable adults with CF. Investigators applying shear rheology experiments in future prospective studies should consider using multiple measurements aiming to increase precision of sputum rheological outcomes.

Severe Asthma Phenotypes Classified by Site of Airway Involvement and Remodeling via Chest CT Scan.

OBJECTIVES: This study aimed to establish a system that can classify severe asthma on the basis of airway remodeling patterns visualizedusing computed tomography (CT) images and to evaluate the clinical characteristics of individual image-based subtypes. METHODS: Chest CT images from severe asthma patients were retrospectively evaluated to classify phenotypes by site of airway involvement and remodeling. The association between radiologic subtypes and clinical characteristics was assessed. RESULTS: Of 91 patients with severe asthma, 74 (81.3%) exhibited abnormal radiologic findings, including bronchial wall thickening (BT), mucus plugging (MP), and bronchiectasis (BE). The severity of BT and the extent of MP were independently associated with peripheral blood eosinophil count (P=.012, r2=0.112) and sputum eosinophil count (P=.022, r2=0.090), respectively. The large-to-medium airway remodeling type, which showed diffuse BT combined with MP and BE, accounted for 44% of patients and revealed higher peripheral blood eosinophil counts than other types. In the small airway remodeling type, which accounted for 6.6% of patients, we observed a higher rate of fixed airflow obstruction, along with a predominance of males and smokers and more frequent use of controller medication than other phenotypes. In 26% of patients with severe asthma, no prominent airway remodeling was observed (near-normal type); the near-normal type required oral corticosteroids less frequently than the large-to-medium airway and small airway remodeling types. CONCLUSIONS: Depending on the site of airway involvement and remodeling pattern, 3 different structural types can be distinguished in chest CT findings from patients with severe asthma. Remodeling in large-to-medium sized airways revealed an association with systemic eosinophilic inflammation in patients with severe asthma.

Factors associated with bronchiectasis in patients with uncontrolled asthma; the NOPES score: a study in 398 patients.

BACKGROUND: Some studies have reported a high prevalence of bronchiectasis in patients with uncontrolled asthma, but the factors associated with this condition are unknown. The objective of this study was to determine the prevalence of bronchiectasis in uncontrolled moderate-to-severe asthma and to identify risk factors and their correlation with bronchiectasis in these patients. METHODS: This is a prospective study of data from consecutive patients with uncontrolled moderate-to-severe asthma. Diagnosis of bronchiectasis was based on high-resolution computed tomography. A prognostic score was developed using a logistic regression model, which was used to determine the factors associated with bronchiectasis. RESULTS: A total of 398 patients (60% with severe asthma) were included. The prevalence of bronchiectasis was 28.4%. The presence of bronchiectasis was associated with a higher frequency of chronic expectoration (OR, 2.95; 95% CI, 1.49-5.84; p = 0.002), greater severity of asthma (OR, 2.43; 95% CI, 1.29-4.57; p = 0.006), at least one previous episode of pneumonia (OR, 2.42; 95% CI, 1.03-5.69; p = 0.044), and lower levels of FeNO (OR, 0.98; 95% CI, 0.97-0.99; p = 0.016). The NOPES score was developed on the basis of these variables (FeNO[cut off point 20.5 ppb], Pneumonia, Expectoration and asthma Severity), and it ranges from 0 to 4 points, where 0 means "no risk" and 4 corresponds to "high risk". The NOPES score yielded an AUC-ROC of 70% for the diagnosis of bronchiectasis, with a specificity of 95%. CONCLUSIONS: Almost a third of the patients with uncontrolled moderate-to-severe asthma had bronchiectasis. Bronchiectasis was related to the severity of asthma, the presence of chronic expectoration, a previous history of pneumonia, and lower levels of FeNO. The NOPES score is an easy-to-use scoring system with a high prognostic value for bronchiectasis in patients with uncontrolled moderate-to-severe asthma.

Linear rheology as a potential monitoring tool for sputum in patients with Chronic Obstructive Pulmonary Disease (COPD).

BACKGROUND: The rheological properties of sputum may influence lung function and become modified in disease. OBJECTIVE: This study aimed to correlate the viscoelastic properties of sputum with clinical data on the severity of disease in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sputum samples from COPD patients were investigated using rheology, simple mathematical modelling and Scanning Electron Microscopy (SEM). The samples were all collected from patients within two days of their admission to Prince Philip Hospital due to an exacerbation of their COPD. Oscillatory and creep rheological techniques were used to measure changes in viscoelastic properties at different frequencies over time. RESULTS: COPD sputum was observed to behave as a viscoelastic solid at all frequencies studied. Comparing the rheology of exacerbated COPD sputum with healthy sputum (not diagnosed with a respiratory disease) revealed significant differences in response to oscillatory shear and creep-recovery experiments, which highlights the potential clinical benefits of better understanding sputum viscoelasticity. A common power law model G(t)=G0(tτ0)-m was successfully fitted to experimental rheology data over the range of frequencies studied. CONCLUSIONS: A comparison between clinical data and the power law index m obtained from rheology, suggested that an important possible future application of this parameter is as a potential biomarker for COPD severity.

Different expression about induced sputum cell sorting in the two main types of chronic obstructive pulmonary disease.

BACKGROUND: The difference in expression of sputum cells types between the two main types of chronic obstructive pulmonary disease (COPD) is largely unknown. This study aims to investigate the difference and then wants to depend on sputum cells sorting to direct the treatment of COPD. METHODS: A total of 218 patients with stable COPD (FEV1 < 80%) were selected. Stable COPD patients (n = 218) were classified as eosinophilic (A phenotype) or noneosinophilic (B phenotype); sometimes, the subjects were separated into cough group (C phenotype) and dyspnea group (D phenotype). Cross-sectional analysis was conducted comparing demographics and clinical characteristics. Receiver-operating characteristic curve was used to assess predictive ability of sputum eosinophils for D phenotype. RESULTS: The A phenotype showed a higher correlation with the patients complaining of presenting with dyspnea on exertion, the dyspnea group (D phenotype). The B phenotype showed a higher prevalence of those who cough and product sputum, this was cough group (C phenotype). Sputum eosinophil and macrophages counts were significantly higher in patients with dyspnea (n = 95) compared to those with cough (P < .05), and neutrophils were significantly lower in patients with dyspnea (n = 95) compared to those with cough (P < .05). Percentage sputum eosinophil count was predictive of dyspnea (D phenotype) COPD with area under curve (AUC) of 0.831 (95% confidence interval (CI) 0.77-0.89; P ≤ .001). Neutrophils were also predictive of dyspnea (D phenotype) COPD with AUC of 0.276 (95% CI 0.204-0.347; P ≤ .001). CONCLUSION: These findings suggest that the morphological phenotypes of COPD show several clinical characteristics and different sputum cell sorting.

A new method for enhanced expectoration of sputum by vibratory stimulation of the cervical trachea.

BACKGROUND: Expectoration of sputum can be difficult for patients with respiratory conditions such as chronic obstructive pulmonary disease, chronic bronchitis, or bronchiectasis because of the effects of decreased pulmonary function, respiratory muscle fatigue, altered sputum properties, and impaired ciliary function. We developed a new method for the vibratory stimulation of the cervical trachea and this study aimed to compare it with the Acapella (a current oscillation device) method. METHODS: Patients with chronic productive cough and difficulty with expectoration were recruited for the study. The tracheal vibration and Acapella methods were applied for 4 weeks each, according to a crossover design with an intervening 4-week washout period. To perform the tracheal vibration method, an electronic artificial larynx (Yourtone®) was applied to the cervical trachea for up to 5minutes. Patient preference for the two devices was determined from the performance scores recorded for each device and by using a visual analogue scale. RESULTS: Twelve patients were recruited in the study. According to the performance scores assigned by the subjects, the tracheal vibration method was effective in 9 patients, while the Acapella method was effective in 10 patients. Both methods were effective in 8 patients, among whom the tracheal vibration method was more effective in 5 patients. Both methods were found to be ineffective in 1 patient. CONCLUSIONS: The tracheal vibration method may be effective at removing central airway sputum and does not require repeated forced expiratory effort, which can otherwise cause exhaustion in patients with decreased lung function. Further investigation is required to confirm its use as a new oscillation technique.

Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor.

Asthma is a chronic airway disease characterized by inflammation, mucus hypersecretion and abnormal airway smooth muscle (ASM) contraction. Bacterial permeability family member A1, BPIFA1, is a secreted innate defence protein. Here we show that BPIFA1 levels are reduced in sputum samples from asthmatic patients and that BPIFA1 is secreted basolaterally from healthy, but not asthmatic human bronchial epithelial cultures (HBECs), where it suppresses ASM contractility by binding to and inhibiting the Ca2+ influx channel Orai1. We have localized this effect to a specific, C-terminal α-helical region of BPIFA1. Furthermore, tracheas from Bpifa1-/- mice are hypercontractile, and this phenotype is reversed by the addition of recombinant BPIFA1. Our data suggest that BPIFA1 deficiency in asthmatic airways promotes Orai1 hyperactivity, increased ASM contraction and airway hyperresponsiveness. Strategies that target Orai1 or the BPIFA1 deficiency in asthma may lead to novel therapies to treat this disease.

Effects of treadmill exercise versus Flutter® on respiratory flow and sputum properties in adults with cystic fibrosis: a randomised, controlled, cross-over trial.

BACKGROUND: Treadmill exercise and airway clearance with the Flutter® device have previously been shown to improve mucus clearance mechanisms in people with cystic fibrosis (CF) but have not been compared. It is therefore not known if treadmill exercise is an adequate form of airway clearance that could replace established airway clearance techniques, such as the Flutter®. The aim of this study was to evaluate respiratory flow, sputum properties and subjective responses of treadmill exercise and Flutter® therapy, compared to resting breathing (control). METHODS: Twenty-four adults with mild to severe CF lung disease (FEV1 28-86% predicted) completed a three-day randomised, controlled, cross-over study. Interventions consisted of 20 min of resting breathing (control), treadmill exercise at 60% of the participant's peak oxygen consumption and Flutter® therapy. Respiratory flow was measured during the interventions. Sputum properties (solids content and mechanical impedance) and subjective responses (ease of expectoration and sense of chest congestion) were measured before, immediately after the interventions and after 20 min of recovery. RESULTS: Treadmill exercise and Flutter® resulted in similar significant increases in peak expiratory flow, but only Flutter® created an expiratory airflow bias (i.e. peak expiratory flow was at least 10% higher than peak inspiratory flow). Treadmill exercise and Flutter® therapy resulted in similar significant reductions in sputum mechanical impedance, but only treadmill exercise caused a transient increase in sputum hydration. Treadmill exercise improved ease of expectoration and Flutter® therapy improved subjective sense of chest congestion. CONCLUSIONS: A single bout of treadmill exercise and Flutter® therapy were equally effective in augmenting mucus clearance mechanisms in adults with CF. Only longer term studies, however, will determine if exercise alone is an adequate form of airway clearance therapy that could replace other airway clearance techniques. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, Registration number # ACTRN12609000168257 , Retrospectively registered (Date submitted to registry 26/2/2009, First participant enrolled 27/2/2009, Date registered 6/4/2009).

Utilidad del esputo inducido en la práctica clínica habitual / Utility of Induced Sputum in Routine Clinical Practice

Objetivos: Determinar la utilidad general y específica (diagnóstica y/o terapéutica) del recuento de las células inflamatorias (RCI) del esputo inducido (EI) en situación de asistencia clínica real. Métodos: Estudio retrospectivo que incluyó a los 171 pacientes que durante un año se les recogió un EI para determinar su RCI en un servicio de Neumología de un hospital de referencia. Observadores independientes al equipo médico habitual establecieron si la información proporcionada por el RCI del EI fue útil en la toma de decisiones diagnósticas y terapéuticas. Resultados: Las causas más frecuentes que motivaron la solicitud del RCI del EI fueron: asma 103 (59,20%); asma de control difícil 34 (19,54%); tos crónica 19 (10,9%), y reflujo gastroesofágico 15 (8,6%). En 115 (67,3%) pacientes el RCI del EI resultó clínicamente útil (valoración general); en 98 (57,3%) proporcionó información diagnóstica, y en 85 (49,7%), información terapéutica relevante. En el asma, asma de control difícil, tos crónica y reflujo gastroesofágico fue útil en el 71,8, el 67,6, el 47,4 y el 60%, respectivamente. Conclusiones: La información proporcionada por el RCI del EI resulta de gran utilidad en la práctica clínica, particularmente en el asma y la tos crónica. Estos resultados podrían proporcionar argumentos para recomendar la incorporación de la técnica en los servicios de Neumología de referencia y en las unidades de excelencia de asma)

Objective: To determine the general and specific utility in diagnosis and/or treatment of induced sputum (IS) inflammatory cell counts in routine clinical practice. Methods: Retrospective study of 171 patients referred for clinical sputum induction over a 1-year period in the pulmonology department of a referral hospital. Independent observers established whether the information provided by IS inflammatory cell count was useful for making diagnostic and therapeutic decisions. Results: The most frequent reasons for determination of IS inflammatory cell count were: asthma 103 (59.20%); uncontrolled asthma 34 (19.54%); chronic cough 19 (10.9%), and gastroesophageal reflux 15 (8.6%). In 115 patients (67.3%) it was generally useful for diagnosis and/or treatment; in 98 patients (57.3%) it provided diagnostic information and in 85 patients (49.7%) it assisted in therapeutic decision-making. In asthma, uncontrolled asthma, chronic cough and gastroesophageal reflux, the results were useful in 71.8%, 67.6%, 47.4% and 60%, respectively. Conclusion: The information provided by IS inflammatory cell count is extremely useful in clinical practice, especially in asthma and chronic cough. These results may justify the inclusion of the IS technique in pulmonology departments and asthma units of referral centers