Differential airway resistome and its correlations with clinical characteristics in Haemophilus- or Pseudomonas-predominant microbial subtypes of bronchiectasis.

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.

A case management model for patients with granulomatous mastitis: a prospective study.

BACKGROUND: Granulomatous mastitis (GM) is a chronic inflammatory mastitis disease that requires long-term treatment and has a high recurrence rate. Case management has been proven to be an effective mechanism in assisting patients with chronic illness to receive regular and targeted disease monitoring and health care service. The aim of this study was to investigate the application of a hospital-to-community model of case management for granulomatous mastitis and explore the related factors associated with its recurrence. METHODS: This was a prospective study on patients with granulomatous mastitis based on a case management model. Data on demographic, clinical and laboratory information, treatment methods, follow-up time, and recurrence were collected and analyzed. The eight-item Morisky Medication Adherence Scale (MMAS-8) was used to investigate patients' adherence to medications. Logistic regression models were built for analysis of risk factors for the recurrence of granulomatous mastitis. RESULTS: By October 2021, a total of 152 female patients with a mean age of 32 years had undergone the entire case management process. The mean total course of case management was 24.54 (range 15-45) months. Almost all the patients received medication treatment, except for one pregnant patient who received observation therapy, and approximately 53.9% of the patients received medication and surgery. The overall recurrence rate was 11.2%, and "high" medication adherence (RR = 0.428, 95% CI 0.224-0.867, P = 0.015) was significantly associated with a lower rate of recurrence, while the rate of recurrence with a surgical procedure + medication was higher than that with medication alone (RR = 4.128, 95% CI 1.026-16.610, P = 0.046). CONCLUSION: A case management model for patients with granulomatous mastitis was applied to effectively monitor changes in the disease and to identify factors associated with disease recurrence. "Low" medication adherence was a significant risk factor for the recurrence of granulomatous mastitis. Patients treated with medication and surgery were more likely to experience recurrence than those treated with medication alone. The optimal treatment approach should be planned for granulomatous mastitis patients, and patient medication adherence should be of concern to medical staff.

Pregnancy Associated Granulomatous Mastitis: Clinical Characteristics, Management, and Outcome.

Background: We have already known that idiopathic granulomatous mastitis (IGM) is a rare benign chronic inflammatory disorder that can clinically mimic breast carcinoma, especially affects parous women of childbearing age, but there is little literature to report about pregnancy associated granulomatous mastitis (PAGM). The aim of our study is to report and describe the clinical signs, managements, clinical course, and clinical outcomes after treatment of PAGM in our hospital. Methods: We retrospectively analyzed 15 pregnant patients who were diagnosed as PAGM in our hospital collected from December 2018 to December 2020 by reviewing medical records and questionnaire survey, including the patients' characteristics, clinical presentations, microbiological workups, tissue pathology, treatment modalities, outcomes, and follow-up data. Results: The mean age of these patients at diagnosis was 30.5 (range 24-35) years. All patients had one birth before, and had at least two gravida times, 6 of them (40%) had three gravida times, and only one of them had four gravida times at diagnosis. The mean weeks of gestational age were 23.7 (range 4-37) weeks. Two patients' BMI were greater than 30, which were considered obese. The mean time to presentation since last delivery was 38.4 (range 19-78) months. All patients had a history of breastfeeding; the average breastfeeding time was 12.97 months. Just 2 of them were diagnosed with lactational mastitis before. One patient smoked before, 1 patient had oral contraceptive pills before, 4 patients had breast trauma recently, 5 patients had positive bacterial culture of pyogenic fluids, 3 patients had nipple retraction, 6 patients had abnormal humoral immunity, shown as elevated C3 or C4, and 2 patients had elevated serum prolactin. All patients presented as a breast mass with pain; two of them had erythema nodosum and oligoarthritis. Nearly all patients had unilateral lesion. The mean follow-up was 11 (range 1-24) months. Thirteen patients gave birth to a healthy baby, and all babies had a healthy growth and development. Almost all patients chose observation during pregnancy. Nine patients demonstrated complete remission, five of them underwent surgery after steroids and/or antibiotics, one patient had observation alone, two chose postpartum steroids alone, and the last one chose postpartum antibiotics alone. The average time to complete remission was 11.2 (range 7-18) months. Conclusions: In general, PAGM is a much rare disorder which has onset during pregnancy, and mainly happens in the second trimester and the third trimester. PAGM patients were all parous women and generally within 5 years of their last pregnancy, also with uncertain etiology and pathogenesis. Observational therapy during pregnancy for PAGM is reliable and feasible.

Decreased Systemic and Airway Sirtuin 1 Expression in Adults With Bronchiectasis.

Aim: Whether accelerated aging, reflected by sirtuin 1 (SIRT1) expression, is implicated in bronchiectasis remains largely unknown. We sought to determine the patterns of SIRT1 and other aging markers in systemic circulation and airways and their expression levels associated with bronchiectasis severity and exacerbation. Methods: We enrolled 132 patients with bronchiectasis and 50 healthy subjects in a prospective cohort study to profile aging markers in systemic circulation and recruited 36 patients with bronchiectasis and 32 disease controls (idiopathic pulmonary fibrosis or tumors) in a cross-sectional study to profile aging markers in bronchial epithelium of both large-to-medium and small airways. We profiled aging marker expression from peripheral blood mononuclear cells and enumerated the positively stained cells for detection of aging marker expression in bronchial epithelium. Results: Compared with healthy controls, the relative telomere length (median: 0.88 vs. 0.99, p = 0.009), SIRT1 (median: 0.89 vs. 0.99, p = 0.002), and Ku80 (median: 0.87 vs. 0.96, p < 0.001) expression levels were consistently lower in the peripheral blood mononuclear cells among patients with bronchiectasis and modestly discriminated patients with bronchiectasis from healthy controls. No remarkable changes in SIRT1, telomere length, or Ku70 were identified at onset of exacerbation. Within the bronchial epithelium, the percentage of positively stained cells was lower for SIRT1 (median: 25.1 vs. 57.2%, p < 0.05) and numerically lower for p16 (median: 40.0 vs. 45.1%) and p21 (median: 28.9 vs. 35.9%) in patients with bronchiectasis than in disease controls (p > 0.05). Conclusion: SIRT1 was downregulated in systemic circulation and bronchiectatic airways, which was independent of disease severity and lung function impairment.

The Role of Epstein-Barr Virus in Adults With Bronchiectasis: A Prospective Cohort Study.

BACKGROUND: Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. METHODS: We collected induced sputum in healthy controls and spontaneous sputum at 3-6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. RESULTS: We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1ß (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor-α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. CONCLUSIONS: Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

BACKGROUND: Exacerbations are crucial events during bronchiectasis progression. OBJECTIVES: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. METHODS: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. RESULTS: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P<.05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P<.05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P=.019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. CONCLUSIONS: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study.

Background: Exacerbations are crucial events during bronchiectasis progression. Objectives: To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. Methods: In this prospective study, we enrolled 108 patients who were followed up every 3-6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. Results: The median exacerbation rate was 2.0 (interquartile range: 1.0-2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76-6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35-4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11-4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P < .05). Sputum interleukin-1ß levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P < .05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P = .019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. Conclusions: Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.

Contexto: Las exacerbaciones son eventos cruciales durante la progresión de la bronquiectasia. Objetivos: Analizar las asociaciones entre el aislamiento de bacterias, virus y virus y bacterias juntas y las exacerbaciones de las bronquiectasias. Métodos: En este estudio prospectivo se incluyó a 108 pacientes a los que se siguió cada 3-6 meses y al comienzo de las exacerbaciones entre marzo de 2017 y noviembre de 2018. La muestra de esputo espontáneo se dividió para la detección de bacterias (cultivo de rutina) y virus (reacción en cadena de la polimerasa cuantitativa). Se evaluaron los síntomas y la función pulmonar durante las exacerbaciones. Resultados: La mediana de la tasa de exacerbación fue de 2,0 (rango intercuartil: 1,0-2,5) por paciente/año. En cualquier visita, los aislamientos de virus (V+) tuvieron lugar con mayor frecuencia durante el inicio de las exacerbaciones (odds ratio [OR]: 3,28; intervalo de confianza del 95% [IC 95%]: 1,76-6,12), al igual que el aislamiento de nuevas bacterias (NB+) (OR: 2,52; IC 95%: 1,35-4,71) y los aislamientos de bacterias y virus juntos (OR: 2,24; IC 95%: 1,11-4,55). Mientras que la coriza parecía más común en las exacerbaciones con V+ que en las exacerbaciones sin aislamientos de patógenos y en aquellas con NB+, los síntomas de las vías respiratorias inferiores fueron más graves en las exacerbaciones con NB+ (p < 0,05). Los niveles de interleucina-1ß en el esputo fueron más altos en las exacerbaciones con NB+ que en las exacerbaciones sin aislamiento de patógenos, y aquellas con V+ (ambos p < 0,05). De manera significativa, más síntomas de coriza se correlacionaron con aislamientos de bacterias y virus juntos durante las exacerbaciones (p = 0,019). Comparados con los V+ en solitario, los aislamientos de bacterias con y sin virus tienden a producir síntomas más graves en las vías respiratorias inferiores, pero no alteran los niveles de citocinas en el esputo durante las exacerbaciones. Conclusiones: Los aislamientos de virus, el aislamiento de nuevas bacterias y el aislamiento de bacterias y virus juntos están asociados a las exacerbaciones de las bronquiectasias. Los síntomas de las exacerbaciones pueden proporcionar información a los médicos sobre los posibles patógenos responsables.

Sputum Exosomal microRNAs Profiling Reveals Critical Pathways Modulated By Pseudomonas aeruginosa Colonization In Bronchiectasis.

Background: Pseudomonas aeruginosa (PA) colonization confers poor prognosis in bronchiectasis. However, the biomarkers and biological pathways underlying these associations are unclear. Objective: To identify the roles of PA colonization in bronchiectasis by exploring for sputum exosomal microRNA profiles. Methods: We enrolled 98 patients with clinically stable bronchiectasis and 17 healthy subjects. Sputum was split for bacterial culture and exosomal microRNA sequencing, followed by validation with quantitative polymerase chain reaction. Bronchiectasis patients were stratified into PA and non-PA colonization groups based on sputum culture findings. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis to explore biological pathways corresponding to the differentially expressed microRNAs (DEMs) associated with PA colonization. Results: Eighty-two bronchiectasis patients and 9 healthy subjects yielded sufficient sputum that passed quality control. We identified 10 overlap DEMs for the comparison between bronchiectasis patients and healthy subjects, and between PA and non-PA colonization group. Both miR-92b-5p and miR-223-3p could discriminate PA colonization (C-statistic >0.60) and independently correlated with PA colonization in multiple linear regression analysis. The differential expression of miR-92b-5p was validated by quantitative polymerase chain reaction (P<0.05), whereas the differential expression of miR-223 trended towards statistical significance (P=0.06). These DEMs, whose expression levels correlated significantly with sputum inflammatory biomarkers (interleukin-1ß and interleukin-8) level, were implicated in the modulation of the nuclear factor-κB, phosphatidylinositol and longevity regulation pathways. Conclusion: Sputum exosomal microRNAs are implicated in PA colonization in bronchiectasis, highlighting candidate targets for therapeutic interventions to mitigate the adverse impacts conferred by PA colonization.

A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge.

Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated with nipple discharge. This study investigated the relationships between ductoscopic image-based indicators and breast cancer risk, and developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge. A total of 879 consecutive inpatients (916 breasts) with nipple discharge who underwent selective duct excision for intraductal neoplasms detected by MD from June 2008 to April 2014 were analyzed retrospectively. A nomogram was developed using a multivariate logistic regression model based on data from a training set (687 cases) and validated in an independent validation set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for the diagnosis of breast cancer. Color of discharge, location, appearance, and surface of neoplasm, and morphology of ductal wall were independent predictors for breast cancer in multivariate logistic regression analysis. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.36. Area under the curve values of 0.812 (95 % confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was obtained in the training and validation sets, respectively. The accuracies of the nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 % in the validation set. We developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge based on MD image findings. This model may aid individual risk assessment and guide treatment in clinical practice.

[Effect of bronchoscopic cryosurgery in twenty-two children with lower airway stenosis].

OBJECTIVE: To analyze the effect and safety of bronchoscopic cryosurgery in children with lower airway stenosis caused by granulation and fiber hyperplasia. METHOD: Twenty-two patients had undergone bronchoscopic examination and cryosurgery, 18 patients with atelectasis caused by Mycoplasma pneumoniae pneumonia, 2 patients with endobronchial tuberculosis (EBTB), 1 patient with atelectasis caused by granulation tissue after bronchial foreign body, and 1 case who had severe dyspnea, with tracheal stenosis after long-term endotracheal intubation during surgery for heart disease. All the patients under went bronchoscopic cryosurgery for several times, 1 case with severe tracheal stenosis was operated by electric coagulation before cryosurgery. Before and after the treatment, all the patients were evaluated based on clinical symptoms, tracheal lumen by bronchoscopy, chest CT for atelectasis and pulmonary function for tracheal stenosis. RESULT: The patients were treated with cryosurgery for 1-4 times. Sixteen cases were markedly improved, clinical symptoms disappeared completely, no granulation and fiber hyperplasia were found during bronchoscopy, and all the atelectasis were cured. After the treatment, the bronchial lumen diameter of the patient with tracheal stenosis was increased from 2 mm to about 5 mm, the tidal volume increased from 3.0 ml/kg to 8.8 ml/kg. Five cases were effectively improved, the clinical symptoms also disappeared, during bronchoscopy and bronchial alveolar lavage (BAL), no granulation and fiber hyperplasia were found, but some distal bronchial tubes were atresia or narrowed, the lumen was patent, the atelectasis recovered partially. In 1 case the treatment was ineffective, as the clinical symptoms and granulation disappeared, but because almost all distal bronchi were atresia or narrow, the lumen was not patent during BAL, there was no change on chest CT. The total effective rate was 21/22 (95.5%). No severe complications occurred during and after the procedures. All the patient were followed up for 1 - 12 months, no case had recurrence. CONCLUSION: Treatment with bronchoscopic cryosurgery is a safe and effective methods to tracheal stenosis caused by granulation tissue and fiber hyperplasia in children.

[Application of bronchoalveolar lavage treatment via bronchoscopy in the management of accidental inhalation of liquid and powdery foreign bodies in children].

OBJECTIVE: To evaluate the effect of bronchoalveolar lavage (BAL) through bronchoscopy in diagnosis and treatment of accidental inhalation of liquid and powdery foreign bodies in children. METHOD: Twenty-one cases of accidental inhalation were classified into the following 4 groups according to the materials inhaled: 3 cases inhaled the lipidic material; 2 cases inhaled chemical material; 15 cases inhaled hydrosoluble materials; 1 case inhaled powdery material. Eighteen cases were hospitalized within 3 days after the accidents, which included 16 cases treated within 1 day in hospital. And 3 cases were hospitalized 3 days after the accident. After hospitalization, all patients were immediately treated with direct aspiration and lavage clearance method through bronchoscopy. The inhaled foreign materials were cleared as soon as possible, which reduced the absorption, stimulation and infection of respiratory mucosa. The therapeutic effect was evaluated by endoscopic findings, clinical manifestation, laboratory examination and chest imaging. At the same time, decision was made on the second BAL and the prognosis was estimated. RESULT: Twenty-one cases had dyspnea of certain degree. The bronchial mucous membrane of all the 21 cases showed hyperemia, edema and exudate attached. Lavage fluid looked like broth and contained much of the inhaled material. After two to five times treatment, 18 cases were cured (86%), but 3 cases died (14%). One of these 3 cases fell into an oil well, 1 into mosquito repellent solution, another into manure pit. The patients who could not survive had severe airway obstruction, which was difficult to clean and made the problem deteriorated progressively. One of the patients was sent to a hospital 3 days after the accident and another case developed fungal infection, pneumothorax and finally respiratory failure. CONCLUSION: BAL through bronchoscopy is necessary for children who accidentally inhaled liquid and powdery materials. This treatment is safe and effective in diagnosis and treatment of such problems in children. The effect of treatment is influenced by types of inhaled material, the time of lavage clearance through bronchoscopy, and certain complications, such as infection etc.

[Balloon dilatation bronchoplasty in management of bronchial stenosis in children with mycoplasma pneumonia].

OBJECTIVE: To assess the efficacy and safety of balloon dilatation through flexible bronchoscopy in the management of inflammatory stenosis of grade 4-5 bronchus. METHOD: Thirty patients with inflammatory bronchial stenosis caused by mycoplasmal pneumonia complicated with pulmonary atelectasis were treated with balloon dilatation through fiberoptic bronchoscopy. Before the procedure and after the last operation, therapeutic effect on pulmonary atelectasis were evaluated with CT and all of the patients were followed-up for 1 - 6 months. RESULT: One to three operations were required to achieve satisfactory dilatation. After balloon dilatation, the average airway diameter increased obviously and the farther airways were opened after the therapy with irrigation. In 25 of 30 cases satisfactory immediate effects were obtained, a narrow airway diameter above expansion significantly increased as compared with preoperative diameter. In 5 children treated with balloon dilatation, the stenosis could not be improved significantly. In 3 patients with hyperplasia of granulation tissue, cryotherapy had to be applied. The operations were ineffective in the other two patients whose course of disease exceeded 3 months. After follow-up periods of 1 - 6 months, chest CT manifestation of expanded sites was improved in 28 patients and atelectasis disappeared. No severe complication was found in any patients. CONCLUSION: Bronchoplasty by balloon dilatation through flexible fiberoptic bronchoscopy is a simple, effective and safe method to treat childhood tracheobronchial stenosis after pulmonary infections.