Bronchoalveolar lavage fluid cytokines and chemokines changes after bronchial thermoplasty in severe asthma.

BACKGROUND: Bronchial thermoplasty (BT) is a non-pharmacological intervention in severe asthma with a well-known mechanism of reducing airway smooth muscle. However, its effect on airway inflammation remains uncertain. OBJECTIVE: To investigate the effect of BT on bronchoalveolar lavage fluid (BALF) cytokines and chemokines in severe asthma patients before BT, after the first BT, and 12 weeks after BT. METHODS: Ten severe asthma patients were recruited, and BALF was obtained from right lower lobe before BT, after the first BT, and 12 weeks after BT. BALF analytes were measured and values were compared among the time points. Lung function, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ) were also measured. RESULTS: Tumor necrosis factor (TNF)-α concentration was significantly decreased after the first BT and significantly increased at 12 weeks after BT. Interleukin-6 (IL-6) and TNF-related apoptosis inducing ligand (TRAIL) concentration were significantly increased at 12 weeks after BT. There were no significant changes in Regulated upon activation, normal T-cell expressed and secreted (RANTES) and transforming growth factor-beta1 (TGF-ß1) concentration over time after BT. At 12 weeks after BT, there were significantly greater improvements in the scores on AQLQ (3.93 ± 0.88 to 5.3 ± 0.99, p = 0.002) and ACT (13.6 ± 3.27 to 19 ± 4.44, p = 0.002). The lung function did not differ significantly between pre- and post-BT. CONCLUSIONS: BT has limited effect on TNF-α, IL-6, TRAIL, RANTES, and TGF- ß1 in BALF suggesting that its clinical benefit is not primarily related to this local airway inflammation. The effect on long-term airway inflammation probably needs further studies.

The Prognostic Predictors of Airway Stenting in Malignant Airway Involvement From Esophageal Carcinoma.

BACKGROUND: In locoregional esophageal carcinoma (EC), airway involvement is the most common route of extraesophageal metastasis. The prognosis remains poor even with a multimodality approach. Although airway stenting is well known for restoration of the airway, the survival benefit is still lacking. METHODS: A total of 37 of patients with airway involvement from EC who underwent airway stenting at a single institution from 2015 to 2020 were retrospectively reviewed. Survival curves after stent placement among different groups were analyzed using Kaplan-Meier method. RESULTS: Of 37 patients, 34 were male, and the mean age was 58.9 years (42 to 80). EC was commonly located at midesophagus (51.4%). The site of airway involvement was left main bronchus (48.6%), trachea (32.4%), multiple sites (16.2%), and right main bronchus (2.7%). The nature of airway involvement was tumor invasion (91.9%), compression (62.2%), and fistula (37.8%). Twenty-three patients (62.2%) had airway involvement at the time of esophageal cancer diagnosis. Only 4 patients underwent esophageal stenting. The median survival time after stent placement was 97 days (5 to 539). Chemotherapy and/or radiotherapy were given before stent placement in 18 patients (48.6%). Treatment-naive before airway stenting and diagnosis of airway involvement at the same time of EC diagnosis were independent predictors for the increased survival after stent placement ( P <0.05). Poststent treatment was associated with improved survival ( P =0.002). CONCLUSION: In patients with malignant airway involvement from EC who underwent airway stenting, the prognostic predictors for improved survival were treatment-naive status, receiving treatment after airway stenting, and early-onset of airway involvement.

Multimodality treatment in immunocompromised patients with severe COVID-19: the role of IL-6 inhibitor, intravenous immunoglobulin, and haemoperfusion.

Cytokine release syndrome (CRS) is known to be associated with severe coronavirus disease 2019 (COVID-19). Multiple anti-inflammatory therapies such as tocilizumab, corticosteroids, intravenous immunoglobulin (IVIG), and haemoadsorption or haemoperfusion have been used to combat this life-threatening condition. However, immunocompromised hosts are often omitted from research studies, and knowledge on the clinical efficacy of these therapies in immunocompromised patients is therefore limited. We report two cases of immunocompromised patients with severe COVID-19-related CRS requiring mechanical ventilation who were treated with multimodality treatment consisting of tocilizumab, IVIG, and haemoperfusion. Within 48 h, both patients showed clinical improvement with PaO2:FiO2 ratio and haemodynamic stability. Both survived to discharge. There were no adverse events following these therapies. In conclusion, combined therapeutic modalities, possibly tailored to individual inflammatory profiles, are promising treatment for severe COVID-19 infection in the immunocompromised host. Timely administration of adjunctive therapies that alleviate overwhelming inflammation may provide the best outcome.

Targeted-Volume Noninvasive Ventilation Reduces Extubation Failure in Postextubated Medical Intensive Care Unit Patients: A Randomized Controlled Trial.

PURPOSE: Till date, the benefit of using noninvasive ventilation (NIV) routinely after extubation to prevent reintubation has been conflicting. We aim to demonstrate the effect of targeted-volume NIV for the prevention of reintubation and extubation failure after planned extubation in medical intensive care unit (ICU) patients. STUDY DESIGN: This was a prospective, randomized controlled study. MATERIALS AND METHODS: Patients on invasive mechanical ventilation for more than 48 hrs for acute respiratory failure, who were ready for extubation, were randomized into targeted-volume NIV (intervention group) or oxygen mask (controlled group) immediately after extubation and continuously for 24 hrs. RESULTS: A total of 58 patients were enrolled in this study. The targeted-volume NIV group was observed to have a trend toward lower reintubation rate within 48 hrs compared to oxygen mask group (0% vs. 17.2%; P = 0.052). Extubation failure rate within 48 hrs was significantly lower in targeted-volume NIV group compared to oxygen mask group (0% vs. 41.38%; P < 0.001). There was a trend toward lower ICU length of stay (6[5] days vs. 10[8] days (median interquartile range [IQR]); P = 0.053) as well as shorter hospital length of stay after extubation (10[19] days vs. 18[15] days (median [IQR]); P = 0.059). There were no differences in the incidence of ventilator-associated pneumonia (VAP)/hospital-acquired pneumonia (HAP) (6.90% vs. 20.69%;P = 0.253) and 28 day-mortality (13.79% vs. 20.69%; P = 0.487). CONCLUSIONS: Our study is the first study to demonstrate the benefit of application of targeted-volume NIV immediately after extubation in reducing extubation failure rate. There was a trend toward lowering reintubation rate and shorter ICU length of stay and hospital length of stay after extubation in mixed medical ICU patients.

Immunoglobulin G4-related disease: a rare steroid-responsive disease.

A 70-year-old man presented with progressive dyspnoea and weight loss. Physical examination revealed only mild pale conjunctiva. The workup showed mild anaemia, mild impaired renal function, and high globulin level. Multiple myeloma was excluded by normal serum protein electrophoresis. The chest radiography and computed tomography (CT) revealed bilateral multifocal patchy infiltration with mediastinal adenopathy. Bronchoscopy was performed. Bronchoalveolar lavage (BAL) fluid examination was negative for infection and malignancy. Tissue pathology revealed diffuse lymphoplasmacytic cell infiltration. Immunohistochemistry revealed positive highlight for CD38, immunoglobulin G (IgG), and IgG4. Serum IgG subclass was requested and showed an IgG4 level of 7230 mg/dL. Examination of bone marrow and submental lymph node pathology were also positive for IgG4. IgG4-related disease with pulmonary involvement was diagnosed. Treatment with prednisolone (30 mg/day) resulted in improvement in his dyspnoea and almost complete resolution of the pulmonary infiltration on repeated CT at 6 month. This case highlighted a rare occurrence of IgG4-related disease which was successfully treated with steroid.