Which inflammatory markers in the bronchial mucosa of asthma patients are associated with decline of lung function during 14 years of prospective follow-up?To address this question, 19 ...mild-to-moderate, atopic asthmatic patients underwent spirometry and bronchoscopy at baseline and after 14 years of follow-up (t=14). Baseline bronchial biopsies were analysed for reticular layer thickness, eosinophil cationic protein (EG2), mast cell tryptase (AA1), CD3, CD4 and CD8. Follow-up biopsies were stained for EG2, AA1, neutrophil elastase, CD3, CD4, CD8, CD20, granzyme B, CD68, DC-SIGN, Ki67 and mucins.Decline in forced expiratory volume in 1 s (FEV1) % predicted was highest in patients with high CD8 (p=0.01, both pre- and post-bronchodilator) or high CD4 counts at baseline (p=0.04 pre-bronchodilator, p=0.03 post-bronchodilator). Patients with high CD8, CD3 or granzyme B counts at t=14 also exhibited faster decline in FEV1 (p=0.00 CD8 pre-bronchodilator, p=0.04 CD8 post-bronchodilator, p=0.01 granzyme B pre-bronchodilator, and p<0.01 CD3 pre-bronchodilator).Long-term lung function decline in asthma is associated with elevation of bronchial CD8 and CD4 at baseline, and CD8, CD3 and granzyme B at follow-up. This suggests that high-risk groups can be identified on the basis of inflammatory phenotypes.
Abstract
Background
There is a considerable diagnostic delay in the diagnosis ‘benign acquired subglottic stenosis in adults’ (SGS, diagnosed by the reference standard, i.e. laryngo- or ...bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of ‘asthma.’ The ‘Expiratory Disproportion Index’ (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients.
Methods
We calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy).
Results
Fifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33–79.18) and 37.94 (32.41–44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86–0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%).
Conclusions
The EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility.
Up to 40% of thoracotomies performed for non-small cell lung cancer are unnecessary, predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion ...(T4). Mediastinoscopy and the novel, minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) target different mediastinal lymph node stations. In addition, EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus.
To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer.
Prospective, nonrandomized multicenter trial performed in 1 referral and 5 general hospitals in the Netherlands. During a 3-year period (2000-2003), 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy. Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative. Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed.
The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients.
Detection of mediastinal tumor invasion (T4) and lymph node metastases (N2/N3) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone.
The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases (36%; 95% confidence interval CI, 27%-46%) compared with either mediastinoscopy alone (20%; 95% CI, 13%-29%) or EUS-FNA (28%; 95% CI, 19%-38%) alone. This indicated that 16% of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy. However, 2% of the EUS-FNA findings were false-positive.
These preliminary findings suggest that EUS-FNA, when added to mediastinoscopy, improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion.
A small-cell lung carcinoma (SCLC) is found in 50% of patients with Lambert-Eaton myasthenic syndrome (LEMS). We evaluated screening to optimize screening strategy for SCLC. It is important to detect ...these tumors early in newly diagnosed patients with LEMS to offer optimal patient treatment.
A large nationwide cohort study of consecutive patients in the Netherlands, seen between 1990 and 2007, were screened for the presence of a tumor using chest x-ray, computed tomography of the thorax (CT-thorax), (18)Ffluorodeoxyglucose positron emission tomography (FDG-PET), bronchoscopy, and/or mediastinoscopy.
SCLC was found in 54 patients, and in 46 patients, no tumor was found during a median follow-up of 8 years (range, 3 to 26 years). All patients with SCLC had a positive smoking history and 86% were still smoking at diagnosis. SCLC was found in 92% of these patients within 3 months and in 96% within a year. At first screening, CT-thorax detected an SCLC in 45 patients (83%), whereas chest x-ray found the tumor in only 23 patients (51%). An SCLC was found during secondary screening in another nine patients (median, 3 months; range, 1 to 41 months). In six patients, a lung tumor was found by CT-thorax or FDG-PET, and in three patients, extrapulmonary metastases were found, initially without identifiable tumor mass on CT-thorax.
In almost all patients (96%), the SCLC was found within 1 year of diagnosis. CT-thorax scans detected most of the tumors (93%) and was far more sensitive than chest x-ray (51%). FDG-PET may have additive value in selected cases. We propose a screening protocol based on CT-thorax and FDG-PET.
Summary Objective To prospectively assess the diagnostic utility of S-adenosylmethionine (AdoMet) and (1→3)-β- d -glucan (β- d -glucan) serum markers for Pneumocystis pneumonia (PCP) in HIV-negative ...patients. Methods HIV-negative, immunocompromised patients suspected of PCP based on clinical presentation and chest imaging were included. PCP was confirmed or rejected by results of direct microscopy and/or real-time PCR on broncho-alveolar lavage (BAL) fluid. Measurement of serum β- d -glucan and AdoMet was performed on serum samples collected at enrollment and during follow-up. Both serum β- d -glucan and AdoMet were assessed for diagnostic accuracy and correlation with clinical and laboratory parameters. Results In 31 patients enrolled (21 PCP-positive, 10 PCP-negative), AdoMet levels did not discriminate between patients with and without PCP. Elevated serum β- d -glucan was a reliable indicator for PCP with a sensitivity of 0.90 and specificity of 0.89 at the 60 pg/ml cut-off. In PCP-positive patients β- d -glucan serum levels decreased during treatment and inversely correlated with Pneumocystis PCR cycle threshold values in BAL fluid. Conclusions The level of serum β- d -glucan – but not AdoMet – was diagnostic for PCP within the clinical context and may serve as marker for pulmonary fungal load and treatment monitoring.
Repeat chest radiograph showed progressive bilateral infiltrations and a right-sided pleural effusion, but unexpectedly C-reactive protein had decreased from 92 mg/L to 32 mg/L. Because our patient ...had a pneumonia that was not resolving with standard antibiotic treatment we widened our differential diagnosis to include antimicrobial failure due to resistant or unusual micro-organisms (such as legionella), infectious complications (such as Staphylococcus aureus empyema), and noninfectious causes such as chemical pneumonitis, eosinophilic pneumonia, vasculitis, or diffuse lung disease.1 We changed the antibiotics to flucloxacillin and ciprofloxacin.
A 42-year old male was referred with a 6-week history of new onset dyspnea. The patient had normal vital signs, no relevant medical history and the only abnormality was a left sided inspiratory ...wheeze. No abnormalities were seen on the chest X-ray. A bronchoscopy was performed which showed a well-circumscribed hypervasculated mass in the left main bronchus. A biopsy was taken, which was complicated after the procedure by dislocation of the mass and coughed up by the patient. Both samples were send for pathologic review. A contrast CT was performed which showed a localized remaining mass in the left main bronchus and no lymph node involvement. Pathological evaluation showed spindle-shaped cell proliferation with mitotic activity in the second larger tissue which could be consistent with an inflammatory myofibroblastic tumor (IMT), whereas the first biopsy sample only showed granulomatous inflammation. Following multidisciplinary review the diagnosis of IMT was made and a treatment plan was decided. Because of the localized position of the mass the patient was treated with laser coagulation via rigid bronchoscopy instead of surgery. Bronchoscopic review afterwards showed complete resolution of the mass and the dyspnea had resolved. This case highlights the difficulty of making the IMT-diagnosis and the option of treating it with laser coagulation via rigid bronchoscopy.
Background:The single-breath N2test (sbN2-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are ...associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD.
Methods:Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean SD age, 63 ± 8 years; exsmokers and smokers; median pack-years, 41 interquartile range, 31 to 51 pack-years). Postbronchodilator spirometry (FEV1, 63 ± 8% of predicted) and sbN2-test (slope of phase III ΔN2, closing capacity CC/total lung capacity TLC percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid.
Results:ΔN2increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN2-test was not associated with any other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between ΔN2and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV1percentage of predicted.
Conclusions:The results of the sbN2-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.
Selected patients with stage III (N2/N3) non-small cell lung cancer (NSCLC) who are downstaged to N0 by chemoradiation therapy might benefit from subsequent surgical resection of the tumor. How ...mediastinal lymph nodes can be best reevaluated is subject of debate. Transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) is a minimally invasive technique to sample mediastinal nodes. We assessed sensitivity and false-negative rate of EUS-FNA for the mediastinal restaging of patients with stage III NSCLC.
Fifty-eight consecutive patients with stage III NSCLC and tissue-proven lymph node metastases N2/N3) who underwent EUS-FNA for restaging purposes after chemoradiation therapy were retrospectively analyzed. Surgical-pathological staging was used as the reference standard for nodal metastases.
EUS-FNA found persistent nodal metastases (N2/N3) in 15 patients (26%). Of the 43 patients without persistent mediastinal metastases at EUS, 33 patients subsequently underwent surgical verification of the mediastinal nodes in whom persistent metastases (yN2/N3) were found in 19 patients (58%), and loco-regional downstaging (yN0) was achieved in the other 14 (42%). The prevalence of persistent nodal metastases in the 48 patients who could be analyzed was 71%. Sensitivity and the false-negative rate of EUS-FNA for mediastinal restaging were 44 and 58%, respectively.
For mediastinal restaging of stage III NSCLC, EUS-FNA is a minimally invasive and safe method to confirm persistent nodal metastases, but this technique has a low negative predictive value and is therefore not useful for the exclusion of mediastinal metastases. Surgical restaging is indicated in the absence of mediastinal metastases at EUS-FNA.
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