Immunotherapy represents a recent milestone in the treatment of lung cancer, particularly with the rapidly expanding development of monoclonal antibodies targeting checkpoint inhibitors in the ...programmed cell death-1 (PD-1) pathway, such as nivolumab and pembrolizumab. Classical auto-immune side effects of these treatments, often called immune-related adverse events (irAEs), can affect multiple organs, including the lungs in which potentially life-threatening pneumonitis may require rapid treatment with high doses of corticosteroids. Nevertheless, the occurrence of severe infections in cancer patients treated with nivolumab, outside the context of immunosuppressive therapy, is a complication that has rarely been reported in the literature.
We report two cases of severe pulmonary infection with unusual microbes, Mycobacterium tuberculosis and Aspergillus fumigatus, in patients treated with nivolumab for non-small cell lung cancer.
Ruling out pulmonary infections may require extensive investigation, as these may have an atypical presentation due to immunomodulation. Furthermore, treating the patient with corticosteroids for immune-related pneumonia could lead to a fatal outcome in this context. This report highlights the importance of excluding the presence of opportunistic infections and tuberculosis before considering immune-related pulmonary toxicity with or without a history of prior corticosteroid use. These cases also emphasize the potential value of tuberculosis screening in patients treated with PD-1 checkpoint inhibitors.
Eosinophils and Lung Cancer: From Bench to Bedside Sibille, Anne; Corhay, Jean-Louis; Louis, Renaud ...
International journal of molecular sciences,
05/2022, Letnik:
23, Številka:
9
Journal Article, Web Resource
Recenzirano
Odprti dostop
Eosinophils are rare, multifunctional granulocytes. Their growth, survival, and tissue migration mainly depend on interleukin (IL)-5 in physiological conditions and on IL-5 and IL-33 in inflammatory ...conditions. Preclinical evidence supports an immunological role for eosinophils as innate immune cells and as agents of the adaptive immune response. In addition to these data, several reports show a link between the outcomes of patients treated with immune checkpoint inhibitors (ICI) for advanced cancers and blood eosinophilia. In this review, we present, in the context of non-small cell lung cancer (NSCLC), the biological properties of eosinophils and their roles in homeostatic and pathological conditions, with a focus on their pro- and anti-tumorigenic effects. We examine the possible explanations for blood eosinophilia during NSCLC treatment with ICI. In particular, we discuss the value of eosinophils as a potential prognostic and predictive biomarker, highlighting the need for stronger clinical data. Finally, we conclude with perspectives on clinical and translational research topics on this subject.
Targeted lung denervation (TLD) is a novel bronchoscopic therapy that disrupts parasympathetic pulmonary nerve input to the lung reducing clinical consequences of cholinergic hyperactivity. The ...AIRFLOW-1 study assessed safety and TLD dose in patients with moderate-to-severe, symptomatic COPD. This analysis evaluated the long-term impact of TLD on COPD exacerbations, pulmonary function, and quality of life over 3 years of follow up.
TLD was performed in a prospective, energy-level randomized (29 W vs 32 W power), multicenter study (NCT02058459). Additional patients were enrolled in an open label confirmation phase to confirm improved gastrointestinal safety after procedural modifications. Durability of TLD was evaluated at 1, 2, and 3 years post-treatment and assessed through analysis of COPD exacerbations, pulmonary lung function, and quality of life.
Three-year follow-up data were available for 73.9% of patients (n = 34). The annualized rate of moderate to severe COPD exacerbations remained stable over the duration of the study. Lung function (FEV
, FVC, RV, and TLC) and quality of life (SGRQ-C and CAT) remained stable over 3 years of follow-up. No new gastrointestinal adverse events and no unexpected serious adverse events were observed.
TLD in COPD patients demonstrated a positive safety profile out to 3 years, with no late-onset serious adverse events related to denervation therapy. Clinical stability in lung function, quality of life, and exacerbations were observed in TLD treated patients over 3 years of follow up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights ► The diagnosis of lung cancer involves the identification and complete classification of malignancy. ► New therapeutic options require specific subtyping of NSCLCs and, increasingly, the ...identification of therapeutically predictive molecular markers, to determine the safest and most effective choice of drugs. ► Small diagnostic sample size and tumour complexity often prevent specific subtyping on morphological grounds alone (NSCLC-NOS). ► Immunohistochemistry can predict the likely NSCLC subtype (squamous cell vs. adenocarcinoma) in most NSCLC-NOS cases. ► Tissue sampling should be maximized whenever feasible and deemed clinically safe, reducing the need for re-biopsy for additional studies. ► Tissue handling, processing and sectioning should minimize wastage and optimize use of tissue for diagnosis.
Dual bronchodilation combining a long-acting β
-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic ...Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 μg and LAMA, glycopyrronium 50 μg (IND/GLY 110/50 μg q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials.
The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 μg q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments.
The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV
; treatment difference, Δ = +71 mL) and transition dyspnoea index (TDI; Δ = 1.09 units), and to LABA or LAMA on trough FEV
(Δ = +101 mL) and a TDI (Δ = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies.
IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments.
ClinicalTrials.gov number: NCT01985334 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Rationale: Targeted lung denervation (TLD) is a novel bronchoscopic treatment for the disruption of parasympathetic innervation of the lungs. Objectives: To assess safety, feasibility, and dosing of ...TLD in patients with moderate to severe COPD using a novel device design. Methods: Thirty patients with COPD (forced expiratory volume in 1 s 30–60%) were 1:1 randomized in a double-blinded fashion to receive TLD with either 29 or 32 W. Primary endpoint was the rate of TLD-associated adverse airway effects that required treatment through 3 months. Assessments of lung function, quality of life, dyspnea, and exercise capacity were performed at baseline and 1-year follow-up. An additional 16 patients were enrolled in an open-label confirmation phase study to confirm safety improvements after procedural enhancements following gastrointestinal adverse events during the randomized part of the trial. Results: Procedural success, defined as device success without an in-hospital serious adverse event, was 96.7% (29/30). The rate of TLD-associated adverse airway effects requiring intervention was 3/15 in the 32 W versus 1/15 in the 29 W group, p = 0.6. Five patients early in the randomized phase experienced serious gastric events. The study was stopped and procedural changes made that reduced both gastrointestinal and airway events in the subsequent phase of the randomized trial and follow-up confirmation study. Improvements in lung function and quality of life were observed compared to baseline values for both doses but were not statistically different. Conclusions: The results demonstrate acceptable safety and feasibility of TLD in patients with COPD, with improvements in adverse event rates after procedural enhancements.
Summary Recently, portable sleep recording devices became an accepted alternative to polysomnography (PSG) for obstructive sleep apnea (OSA) diagnosis in patients with a high pre-test probability of ...moderate to severe OSA but home polysomnography (H-PSG) was not recommended because there were insufficient data. The present review has analysed six prospective randomized crossover studies comparing H-PSG to in-lab PSG. These studies convincingly showed that H-PSG allows complete sleep evaluation. The quality of patients' sleep tends to be better at home. H-PSG is accurate for OSA diagnosis and the failure rate is low despite the absence of supervision. In addition, it could offer a final and comprehensive diagnosis for many other sleep disorders. It is also likely that H-PSG can reduce PSG-related costs but complete cost-effectiveness analyses are not yet available. Recently, remotely attended H-PSG via telemonitoring has been tested and may reduce H-PSG failure rate. In conclusion, H-PSG can be used to rule-in and rule out OSA in suspected patients, even in the presence of co-morbidities and is an alternative when simplified sleep testing is negative. Future developments should target simplification of technical aspects of H-PSG, together with remote monitoring, in order to obtain good quality H-PSG performed in adequate conditions.
Radial endobronchial ultrasonography miniprobe (rEBUS-MP) is a technique that has increased the diagnostic yield of bronchoscopic occult pulmonary lesions. The purpose of this study was to identify ...computed tomography (CT) characteristics affecting the success rate of rEBUS-MP in the evaluation of these pulmonary lesions.
Our study encompassed a retrospective review of all consecutive patients who underwent a rEBUS-MP examination between January 2011 and December 2013. CT characteristics including lesion size, lesion location, and bronchus sign were analyzed against two defined outcomes (visualization yield and diagnostic yield). Univariate analysis was employed to examine the individual effects of each CT parameter on visualization yield and diagnostic yield. Multivariate logistic regression was performed to identify significant predictors of diagnostic yield.
Seven hundred and sixty lesions (760 patients) were included. The mean ± SD longest lesion diameter was 43 ± 2 mm. rEBUS-MP could visualize 83% and a definitive diagnosis was established in 62%. In a multivariate analysis, longest lesion diameter greater than 20 mm (odds ratio OR: 1.97 and p = 0.036), distance lesion to secondary or tertiary carina greater than 40 mm (OR: 0.60 and p=0.016), and lobar segment (1, 3, or 6, respectively) were determined to be significant factors predicting diagnostic yield. Bronchus sign was the only parameter that indirectly influenced the diagnostic yield through enhancing visualization yield (p < 0.001).
Multivariate analysis revealed that lesion size, distance to carina, and segment were predictors of diagnostic yield. The presence of a bronchus sign substantially increased the diagnostic yield through the visualization yield.
Background: The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the ...HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ). Methods: The kinetics of PETCO2 during the HPTest were mathematically modeled and compared between 37 HVS patients (NQ ≥23/64) and 37 healthy controls (NQ <23/64) matched for gender, age, and body dimensions. AUC values with sensitivity and specificity were calculated, and analysis was monitored in a validation cohort of 152 routine HPTests. Results: A threshold value of a less than 12.8 mmHg increment of PETCO2 at the 5th minute of the recovery phase of the HPTest diagnosed HVS patients with excellent sensitivity (0.92) and specificity (0.84). These results were confirmed in the validation cohort, highlighting the presence of 24% false positives/negatives when diagnosing on the basis of complaints in the NQ. Conclusions: For HVS diagnosis, we suggest considering the HPTest, which can more reliably reflect the mechanisms of CO2 homeostasis and the response of the respiratory center to a stimulus, regardless of the subjective onset of symptoms.
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