Thoracic Society of Australia and New Zealand position statement: The safe clinical use of sputum induction for bio-sampling of the lower airways in children and adults.

Sputum induction is widely used in clinical settings for collection of biological samples from the lower airways. However, in recent years sputum induction has been associated with serious adverse events and even death. This position statement was commissioned by the Thoracic Society of Australia and New Zealand to address major adverse events of two deaths associated with sputum induction that have occurred in Australia in 2021, and outlines best practice for the safe use of sputum induction. The statement resulted from systematic literature searches by a multi-disciplinary group including respiratory physicians, nurses and physiotherapists (paediatric and adults focused). Consumers had input to an advanced draft of the position statement. The position statement covers indications for sputum induction, informed consent, scope of practice of personnel administering the procedure, infection control considerations, details about the sputum induction procedure, safety considerations and risk assessment in clinical settings.

Sputum induction and its diagnostic applications in inflammatory airway disorders: a review.

Sputum induction is a technique that covers the induction and the subsequent processing of the expectorate primarily for the analysis of cells and different inflammatory biomarkers present in the airways to further understand the pathophysiology of different inflammatory respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD) as well as the diagnosis of lung diseases such as lung cancer, tuberculosis, and Pneumocystis jirovecii pneumonia. It is a non-invasive, safe, cost-effective, and reliable technique reported to exhibit a high success rate. However, due to being technically demanding and time-consuming and having the need of employing trained staff, this technique is only used in restricted research centres and in limited centres of clinical use. When the sputum is collected after induction, the primary goal is to obtain a differential cell count and evaluate the molecular biomarkers of airway inflammation such as eosinophil cationic protein, eosinophil-derived neurotoxin, major basic protein, tryptase, cytokine production [e.g., interleukin (IL)-5], albumin, and fibrinogen. In addition, cytospins from the processed sputum are used for immunocytochemical staining of cellular products such as EG-2 reactive protein, granulocyte-macrophage colony-stimulating factor, tumour necrosis factor alpha, and IL-8 that play significant roles in understanding the pathophysiology of inflammatory airway diseases. Nowadays, this technique can be further used by performing an additional analysis such as flow cytometry and in situ hybridisation on the sputum supernatant to investigate more the immune response and pathophysiological process of such various respiratory diseases. In addition, the application of sputum fluid phase to assess the biomarkers could be used more routinely in pathological laboratories for diagnosing lung cancer, COPD, and asthma as well as for monitoring lung cancer progression and asthma and COPD treatment, allowing for early detection and a better treatment provided by the clinicians.

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma: Predictors of Bronchial Eosinophilia.

Purpose: The objectives of this study were, for patients attending a specialist asthma clinic at a tertiary care hospital, to determine, from sputum induction (SI), proportions of bronchial inflammatory phenotypes, demographic, clinical and functional characteristics of each phenotype, and the most accessible non-invasive inflammatory marker that best discriminates between phenotypes. Patients and Methods: Included were 96 patients with asthma, attending a specialist asthma clinic at a tertiary care hospital, who underwent testing as follows: SI, spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophilia, total immunoglobulin E (IgE), and a skin prick test. Results: SI phenotypes were 46.9% eosinophilic, 33.3% paucigranulocytic, 15.6% neutrophilic, and 4.2% mixed. No significantly different clinical or functional characteristics were observed between the phenotypes. A positive correlation was observed between SI eosinophilia and both emergency visits in the last 12 months (p = 0.041; r = 0.214) and FeNO values (p = 0.000; r = 0.368). Blood eosinophilia correlated with SI eosinophilia (p = 0.001; r = 0.362) and was the best predictor of bronchial eosinophilia, followed by FeNO, and total blood IgE (area under the receiver operating characteristic curve (AUC-ROC) 72%, 65%, and 53%, respectively), although precision was only fair. Conclusion: In consultations for severe asthma, the most frequent phenotype was eosinophilic. Peripheral blood eosinophilia is a reliable marker for discriminating between different bronchial inflammatory phenotypes, is useful in enabling doctors to select a suitable biologic treatment and so prevent asthma exacerbation, and is a better predictor of bronchial eosinophilia than FeNO and IgE values.

Asthma inflammatory phenotypes on four continents: most asthma is non-eosinophilic.

BACKGROUND: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK). METHODS: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum. RESULTS: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda. CONCLUSIONS: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally.

The spectrum of tuberculosis described as differential DNA methylation patterns in alveolar macrophages and alveolar T cells.

BACKGROUND: Host innate immune cells have been identified as key players in the early eradication of Mycobacterium tuberculosis and in the maintenance of an anti-mycobacterial immune memory, which we and others have shown are induced through epigenetic reprogramming. Studies on human tuberculosis immunity are dominated by those using peripheral blood as surrogate markers for immunity. We aimed to investigate DNA methylation patterns in immune cells of the lung compartment by obtaining induced sputum from M. tuberculosis- exposed subjects including symptom-free subjects testing positively and negatively for latent tuberculosis as well as patients diagnosed with active tuberculosis. Alveolar macrophages and alveolar T cells were isolated from the collected sputum and DNA methylome analyses performed (Illumina Infinium Human Methylation 450 k). RESULTS: Multidimensional scaling analysis revealed that DNA methylomes of cells from the tuberculosis-exposed subjects and controls appeared as separate clusters. The numerous genes that were differentially methylated between the groups were functionally connected and overlapped with previous findings of trained immunity and tuberculosis. In addition, analysis of the interferon-gamma release assay (IGRA) status of the subjects demonstrated that the IGRA status was reflected in the DNA methylome by a unique signature. CONCLUSIONS: This pilot study suggests that M. tuberculosis induces epigenetic reprogramming in immune cells of the lung compartment, reflected as a specific DNA methylation pattern. The DNA methylation signature emerging from the comparison of IGRA-negative and IGRA-positive subjects revealed a spectrum of signature strength with the TB patients grouping together at one end of the spectrum, both in alveolar macrophages and T cells. DNA methylation-based biosignatures could be considered for further development towards a clinically useful tool for determining tuberculosis infection status and the level of tuberculosis exposure.

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.

The lung microbiota in children with cystic fibrosis captured by induced sputum sampling.

BACKGROUND: Spatial topography of the cystic fibrosis (CF) lung microbiota is poorly understood in childhood. How best to sample the respiratory tract in children for microbiota analysis, and the utility of microbiota profiling in clinical management of early infection remains unclear. By comparison with bronchoalveolar lavage (BAL), we assessed the ability of induced sputum (IS) sampling to characterise the lower airway microbiota. METHODS: Sample sets from IS and two or three matched BAL compartments were obtained for microbiota analysis as part of the CF-Sputum Induction Trial (UKCRN_14615, ISRCTNR_12473810). Microbiota profiles and pathogen detection were compared between matched samples. RESULTS: Twenty-eight patients, aged 1.1-17.7 years, provided 30 sample sets. Within-patient BAL comparisons revealed spatial heterogeneity in 8/30 (27%) sample sets indicating that the lower airway microbiota from BAL is frequently compartmentalised in children with CF. IS samples closely resembled one or more matched BAL compartments in 15/30 (50%) sets, and were related in composition in a further 9/30 (30%). IS detected 86.2% of the Top 5 genera found across matched BAL samples. The sensitivity of IS to detect specific CF-pathogens identified in matched BAL samples at relative abundance ≥5% varied between 43 and 100%, with negative predictive values between 73 and 100%. CONCLUSIONS: Spatial heterogeneity of the lower airway microbiota was observed in BAL samples and presents difficulties for consistent lung sampling. IS captured a microbiota signature representative of the lower airway in 80% of cases, and is a straightforward, non-invasive intervention that can be performed frequently to aid pathogen diagnosis and understand microbiota evolution in children with CF.

DNA methylome-based validation of induced sputum as an effective protocol to study lung immunity: construction of a classifier of pulmonary cell types.

Flow cytometry is a classical approach used to define cell types in peripheral blood. While DNA methylation signatures have been extensively employed in recent years as an alternative to flow cytometry to define cell populations in peripheral blood, this approach has not been tested in lung-derived samples. Here, we compared bronchoalveolar lavage with a more cost-effective and less invasive technique based on sputum induction and developed a DNA methylome-based algorithm that can be used to deconvolute the cell types in such samples. We analysed the DNA methylome profiles of alveolar macrophages and lymphocytes cells isolated from the pulmonary compartment. The cells were isolated using two different methods, sputum induction and bronchoalveolar lavage. A strong positive correlation between the DNA methylome profiles of cells obtained with the two isolation methods was found. We observed the best correlation of the DNA methylomes when both isolation methods captured cells from the lower parts of the lungs. We also identified unique patterns of CpG methylation in DNA obtained from the two cell populations, which can be used as a signature to discriminate between the alveolar macrophages and lymphocytes by means of open-source algorithms. We validated our findings with external data and obtained results consistent with the previous findings. Our analysis opens up a new possibility to identify different cell populations from lung samples and promotes sputum induction as a tool to study immune cell populations from the lung.

Elevated serum calprotectin (S100A8/A9) in patients with severe asthma.

OBJECTIVE: Asthma is a heterogeneous disease consisting of several inflammatory phenotypes of which neutrophilic asthma is associated with poorer responses to classic therapies, namely (inhaled) corticosteroids. The development of targeted therapies requires the identification of biomarkers to distinguish these phenotypes. Currently, we lack validated biomarkers for non-eosinophilic asthma. The aim of this study is to examine serum calprotectin (SC) in asthmatics and its potential as biomarker for neutrophilic asthma. METHODS: Hundred-seventeen severe asthmatics were referred for sputum induction and data were obtained from their medical records. To evaluate the association between SC and asthma phenotypes, patients were divided into subgroups based on sputum cell count (3% eosinophils and 61% neutrophils). Additionally, SC levels of asthmatics were compared with these of patients with chronic obstructive pulmonary disease, non-cystic fibrosis bronchiectasis and healthy controls. RESULTS: Asthmatics (n = 45) had significantly higher levels of SC than healthy controls. No significant differences were found between the different asthma phenotypes and in comparison with COPD patients. SC was significantly higher in asthmatics with a lower FEV1/FVC ratio (<70) and non-significantly elevated SC levels were seen in asthmatics with frequent exacerbations (>2 in the last year). CONCLUSION: In conclusion, there was no difference in SC levels between the different inflammatory subtypes in asthmatics. Nevertheless, severe asthmatics seemed to have higher SC levels suggesting that SC may be a marker of disease severity rather than a marker for specific inflammatory subtypes in asthmatics. Further research in larger cohorts is necessary to validate SC as biomarker in severe asthmatics.

The diagnostic yield and safety of sputum induction in suspected pulmonary tuberculosis: The experience of a single tertiary care center in Saudi Arabia.

Background: Sputum smear microscopy examination and culture for tuberculosis (TB) remain a fundamental tool of diagnosis but may be negative up to 50% case of active pulmonary TB. Bronchoscopy to obtain sputum is invasive and not readily available. Alternative methods of obtaining sputum specimens are crucial in suspected pulmonary TB cases who are unable to expectorate. In this context, it may be beneficial to stimulate sputum production by administering a mist of hypertonic saline produced by ultrasonic nebulization. The aims of the study are to describe the experience of a tertiary center in Saudi Arabia with sputum induction (SI) for the investigation of patients suspected to have sputum scare TB. Methods: A retrospective cohort study was performed. All patients suspected of sputum scare TB and investigated with SI were included. Standard descriptive statistics were used. Categorical data presented as frequency were compared using the Chi square test. Continuous data presented as mean ± standard deviation were compared using Student's t test. Sensitivity, specificity, and predictive values were calculated. Results: Of 252 patients with suspected TB who underwent SI, 78 (31%) were ultimately diagnosed to have TB. Culture of induced sputum confirmed the diagnosis of TB in 44 (56.4%) of these patients. However, the diagnosis of TB would have been missed in 13.5% of the cohort if no further investigations were done. The incidence of complications was low. No patients required hospitalization or specialist intervention. Conclusions: SI is safe well tolerated and inexpensive. It may reduce the need for bronchoscopy in patients with suspected sputum scare TB. However, around 20% of TB can be missed by SI unless further investigations are performed. Hence, patients suspected to have sputum scare TB in whom the risk of bronchoscopy is high, a clinical decision on the appropriateness of empirical therapy is often required.

Multidisciplinary consensus on sputum induction biosafety during the COVID-19 pandemic.

Sputum induction (SI) is the gold standard approach to the non-invasive study of airway inflammation. The differential count of inflammatory cells for SI allows patients with asthma to be classified according to inflammatory phenotypes and predicted therapeutic responses. Since SI involves the generation of aerosols, there is a need to establish a protocol to ensure biosafety in clinical practice during the current COVID-19 pandemic. The multidisciplinary consensus on SI described in this article was developed by 22 experts in SI from different Spanish hospitals who drew on available scientific evidence in achieving consensuated opinions, compiled by means of an electronic survey. We hope that these unified criteria and recommendations will guide health professionals in implementing SI sampling and processing procedures as safely as possible during the COVID-19 pandemic.

The yield of Acid-Fast Bacilli (AFB) and tuberculosis (TB) culture in the microbiologic diagnosis of childhood tuberculosis using sputum induction: A randomized controlled trial with interrupted time series

@#<p style="text-align: justify;"><strong>Objectives:</strong> This study aims to determine the diagnostic yield and safety of sputum induction with hypertonic saline in the microbiologic confirmation of childhood tuberculosis (TB) in a tertiary hospital in the Philippines.</p><p style="text-align: justify;"><strong>Methods:</strong> This is a randomized controlled trial with an interrupted time series in the control group. One hundred twelve (112) pediatric patients (4-18 years old) with clinical findings suggestive of TB were enrolled in the study. Patients were randomized into two groups composed of 56 patients each. Group A patients underwent sputum induction. Group B patients underwent spontaneous expectoration followed by sputum induction. The microbiologic yield for acid-fast bacilli and TB culture were determined and analyzed.</p><p style="text-align: justify;"><strong>Results:</strong> Among the patients randomized to Group A, microbiologic confirmation for TB was 8/56 patients (14.3%) after sputum induction. For patients randomized to Group B, microbiologic yield was 4/56 patients (7.1%) from spontaneous expectoration; after sputum induction, the microbiologic yield increased to 5/56 patients (8.9%). There is insufficient evidence of statistical significance in microbiologic yield on parallel analysis of the two separate groups (p=0.22). Furthermore, for patients randomized to Group B, the increase in microbiologic yield after sputum induction compared to spontaneous expectoration did not reach statistical significance (p=1.000). The procedure was well-tolerated among children; no serious adverse events were observed.</p><p style="text-align: justify;"><strong>Conclusion:</strong> Sputum induction is a feasible and safe method of specimen collection for microbiologic diagnosis of TB among children. While the microbiologic yield increased after sputum induction compared to spontaneous expectoration, the additional yield does not seem to be significant.</p>

Inflammatory Subtypes in Classic Asthma and Cough Variant Asthma.

BACKGROUND: Measurement of sputum is used to define airway inflammatory phenotypes. Cough variant asthma (CVA) is considered to be the initial stage of classic asthma (CA). The aim of this study was to describe the association between the different subtypes of CVA and CA. METHODS: A total of 459 patients with CVA and CA were screened for the study. All included patients performed spirometry, underwent a bronchial challenge with methacholine and induced sputum according to the guidelines. RESULTS: A higher frequency of female patients were found with CVA and the eosinophilic airway inflammation of CVA than in CA and the noneosinophilic airway inflammation of CA (p=0.004 and p=0.024, respectively). Bronchial hyper-responsiveness (BHR) was lower in eosinophilic CVA and CA (p=0.006), while no difference was found in noneosinophilic CVA and CA. Association between the percentage of sputum eosinophils and the FEV1 level fell below 20% of the baseline value (PD20) in CVA and CA (r= -0.1245, p=0.0357 and r= -0.2148, p=0.0014, respectively). CONCLUSION: Eosinophilia may be associated with more severe disease, yet there was no difference in spirometry between the eosinophilic and noneosinophilic groups, and the BHR difference was not dramatic.

Randomized trial of physiotherapy and hypertonic saline techniques for sputum induction in asthmatic children and adolescents

OBJECTIVES: This study aimed to analyze the efficiency of physiotherapy techniques in sputum induction and in the evaluation of pulmonary inflammation in asthmatic children and adolescents. Although hypertonic saline (HS) is widely used for sputum induction (SI), specific techniques and maneuvers of physiotherapy (P) may facilitate the collection of mucus in some asthmatic children and adolescents. METHODS: A randomized crossover study was performed in patients with well-controlled asthma, and 90 sputum samples were collected. Children and adolescents were assessed using spirometry and randomized at entry into one of three sputum induction techniques: (i) 3% hypertonic saline - HS technique; (ii) physiotherapy (oscillatory positive expiratory pressure, forced expiration, and acceleration of expiratory flow) - P technique; and (iii) hypertonic saline + physiotherapy - HSP technique. ClinicalTrials.gov: NCT03136042. RESULTS: The total cells (mL) and the percentage (%) of differential inflammatory cells were similar in all techniques. The sputum weight (g) in the HSP technique was significantly higher than that in the HS technique. In all techniques, the percentage of viable cells was >50%, and there was no difference between the HS and P techniques. Moreover, sputum induction did not cause any alterations in the pulmonary function of patients. CONCLUSION: The physiotherapy sputum collection technique was effective in obtaining viable cells from mucus samples and yielded the same amount of sputum as the gold standard technique (hypertonic saline). In addition, the physiotherapy maneuvers were both safe and useful for sputum induction in asthmatic children and adolescents with well-controlled asthma.

Detecting respiratory infection in children with cystic fibrosis: Cough swab, sputum induction or bronchoalveolar lavage.

Young children with cystic fibrosis (CF) are generally very well, cough free and non-productive, and are often incapable of spontaneously expectorating sputum even if actively coughing during an exacerbation. Obtaining a meaningful airway sample for microbiological analysis is therefore problematic, yet essential if lower airway infection is to be detected and adequately treated. Recently there has been increasing interest in the use of sputum-induction in young children with CF, as a simple, cost effective, well tolerated and frequently repeatable approach to sampling the lower airway, and the relative merits of this approach to bacterial sampling are discussed. Culture-independent microbiology has increased our understanding of the respiratory microbiota and has challenged the current paradigm of "single pathogen causes disease". Understanding how to diagnose infection using these new, highly sensitive technologies will be important. How we should best intervene to optimise, manipulate and prevent disruption of the respiratory microbiota is likely to greatly influence how we manage infection in the future.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma.

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION: Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Alternative sputum collection methods for diagnosis of childhood intrathoracic tuberculosis: a systematic literature review.

BACKGROUND: Diagnosis of intrathoracic tuberculosis (ITB) is limited in children partly by their difficulty to produce sputum specimen. OBJECTIVE: To systematically review the detection yields of mycobacterial culture and Xpert MTB/RIF from induced sputum (IS), nasopharyngeal aspirate (NPA) and gastric aspirate (GA) in children with presumptive ITB. DESIGN: Pubmed, Embase and Biosis databases and grey literature were searched. Randomised controlled trials, cohort, cross-sectional or case control studies using IS, GA and NPA for diagnosis of ITB published between January 1990 and January 2018 were included. Data were extracted on study design, case definition of presumptive ITB, sample collection methods, outcome measures and results. RESULTS: 30 studies were selected, including 11 554 children. Detection yields for culture ranged between 1% and 30% for IS, 1% and 45% for GA and 4% and 24% for NPA. For Xpert MTB/RIF, it was between 2% and 17% for IS, 5% and 51% for GA and 3% and 8% for NPA. There was a tendency of better yields with IS when the pretest probability of ITB was low to moderate and with GA when it was high. Sampling a second specimen contributed for 6%-33% of the cumulative yield and combination of different methods significantly increase the detection yields. CONCLUSIONS: Despite the important study heterogeneity, any of the specimen collection methods offers good potential to confirm childhood ITB. However, their operational challenges were poorly evaluated. In the absence of a sensitive non-sputum based test, only a minority of children with ITB can be confirmed.

Metabolomic Analysis of Serum Glycerophospholipid Levels in Eosinophilic and Neutrophilic Asthma / 生物医学与环境科学（英文）

OBJECTIVE@#To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis.@*METHODS@#Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis.@*RESULTS@#The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%.@*CONCLUSION@#Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.

Incremental yield and cost of urine Determine TB-LAM and sputum induction in seriously ill adults with HIV.

BACKGROUND: Tuberculosis is a major cause of mortality among HIV-infected inpatients, and the World Health Organization (WHO) recommends an algorithm to improve diagnosis. The urine lateral flow lipoarabinomannan (LAM) and sputum Xpert MTB/RIF tests are promising tools, but the optimal diagnostic algorithm is unclear. METHODS: This prospective cohort study enrolled HIV-positive inpatients with cough and WHO danger signs. The Xpert MTB/RIF test and mycobacterial culture were performed on sputum using sputum induction when necessary, and the LAM test was performed on stored urine. Tuberculosis was diagnosed by culture from any site. The diagnostic accuracy and costs of testing were determined for single and combined tests. RESULTS: Tuberculosis was confirmed in 169 of 332 patients (50.9%). The yield of LAM, Xpert MTB/RIF on spontaneous sputum (Xpert Spot), and Xpert MTB/RIF on spontaneous or induced sputum (Xpert SI) was 35.5%, 23.1%, and 90.5%, respectively. When LAM was placed before Xpert Spot and Xpert SI in an algorithm, the yield was 50.9% and 92.3%, respectively. Adding culture to Xpert MTB/RIF only increased the yield by 1.2% and 2.7%, respectively. Use of the LAM test reduced costs. CONCLUSIONS: Sputum induction is important to increase the yield of Xpert MTB/RIF for seriously ill patients with HIV and cough. LAM testing has little effect on yield when sputum induction is available, but reduces costs and may have other benefits.

Loss of bronchoprotection to Salbutamol during sputum induction with hypertonic saline: implications for asthma therapy.

BACKGROUND: Sputum induction with hypertonic saline in obstructive airway diseases is generally safe. However, saline induces bronchoconstriction in some patients despite pre-medication with Salbutamol. Our objectives were to investigate the predictors of failure of Salbutamol to protect against saline-induced-bronchoconstriction in patients with asthma and COPD and to evaluate implications for asthma therapy. METHODS: Retrospective survey on a database of 3565 patients with obstructive airway diseases who had sputum induced with hypertonic saline. The effect of baseline FEV1, bronchitis and concomitant medication on saline-induced-bronchoconstriction (≥ 15% drop in FEV1) were examined by logistic regression analysis. A subgroup had this re-examined 8-12 weeks after decreasing long-acting-beta-2-agonist dose or after adding Montelukast, which included an assessment of mast cell activity in sputum. RESULTS: 222 (6.2%) patients had saline-induced-bronchoconstriction despite pre-treatment with inhaled Salbutamol. Baseline airflow obstruction (FEV1% predicted < 60% OR 3.29, p < 0.001) and long-acting-beta-agonist use (OR 2.02, p = 0.001), but not bronchitis, were predictors of saline-induced-bronchoconstriction, which decreased when long-acting-beta-agonist dose was decreased. Refractoriness to subsequent bronchodilation was associated with mast cell activity and was attenuated by Montelukast. CONCLUSION: Sputum induction with saline provides information on bronchitis and additional physiological data on tolerance to beta-agonists and mast cell activity that may have implications for clinical therapy.