Inflammasome - IL-1 - Th17 response in allergic lung inflammation.

J Mol Cell Biol. 2011 Dec 6;

Authors: Besnard AG, Togbe D, Couillin I, Tan Z, Zheng SG, Erard F, Le Bert M, Quesniaux V, Ryffel B

Abstract
Allergic asthma has increased dramatically in prevalence and severity over the last three decades. Both clinical and experimental data support an important role of Th2 cell response in the allergic response. Recent investigations revealed that airway exposure to allergen in sensitized individuals causes the release of ATP and uric acid activating the NLRP3 inflammasome complex and caspase-1 cleaving pro-IL-1β to mature IL-1β. The production of pro-IL-1β requires a TLR4 signal which is provided by the allergen. IL-1β creates a pro-inflammatory milieu with the production of IL-6 and chemokines which mobilize neutrophils and enhance Th17 cell differentiation in the lung. Here, we review our results showing that NLRP3 inflammasome activation is required to develop allergic airway inflammation in mice and that IL-17 and IL-22 production by Th17 plays a critical role in established asthma. Therefore, inflammasome activation leading to IL-1β production contributes to the control of allergic asthma by enhancing Th17 cell differentiation.

PMID: 22147847 [PubMed - as supplied by publisher]

OBJECTIVE. The purposes of our study were to evaluate ¹⁸F-FDG PET findings of ground-glass opacity (GGO) nodules and to determine the value of FDG PET for the preoperative staging of lung cancer manifesting predominantly as GGO.

MATERIALS AND METHODS. Eighty-nine patients (46 men and 43 women; mean [± SD] age, 62.4 ± 7.2 years [range, 33–81 years] and 61.7 ± 6.7 years [range, 34–75 years], respectively) with 134 GGO nodules (56 single and 78 multiple) who underwent CT and FDG PET before surgery were included. CT and PET findings were assessed in terms of lesion size, GGO percentage, multiplicity, and maximum standardized uptake value (SUV_max). SUV_max was correlated with lesion size and GGO percentage using linear regression. The SUV_max and hypermetabolism rates of solitary and multiple GGO nodules were compared using the Student t test or Fisher exact test. Lymph node and distant organ metastasis staging by FDG PET were correlated with histopathologic findings.

RESULTS. SUV_max was positively correlated with lesion size (mean, 14.5 mm; range, 5–37 mm) (r = 0.6705; p < 0.0001) and was negatively correlated with GGO percentage (mean, 77%; range, 50–100%) (r = –0.7465; p < 0.0001). Solitary nodules showed higher hypermetabolism rates (73% [41/56]) than did multiple nodules (27% [21/78]) (p = 0.0001), but SUV_max was not significantly different between solitary and multiple nodules. There was no true-positive interpretation of nodal or distant metastasis from GGO nodules by FDG PET.

CONCLUSION. FDG PET showed no clear advantage for the staging of lung cancer with predominant GGO because of the low incidences of nodal and distant metastasis.

OBJECTIVE. The purpose of this study was to compare the predictive capabilities of diffusion-weighted MRI (DWI) and ¹⁸F-FDG PET/CT for tumor response to therapy and survival in patients with non–small cell lung cancer (NSCLC) receiving chemoradiotherapy.

SUBJECTS AND METHODS. The study included 64 patients with NSCLC diagnosed as stage III who underwent pretherapeutic DWI and FDG PET/CT and were treated with chemoradiotherapy. For quantitative prediction, apparent diffusion coefficient (ADC) for DWI and maximum standardized uptake value (SUV_max) for PET/CT were measured at all targeted lesions and averaged to obtain final values for each patient. To evaluate the predictive capability of either index for distinguishing partial response and nonresponse (stable or progressive disease) groups, receiver operating characteristic analysis was performed, and sensitivity, specificity, and accuracy of the two modalities were compared using the McNemar test. Finally, overall and progression-free survival curves divided by the corresponding threshold value were compared by means of the log-rank test.

RESULTS. The area under the curve (A_z) for ADC (A_z = 0.84) was significantly larger than that for SUV_max (A_z = 0.64, p < 0.05). The application of feasible threshold values resulted in specificity (44.4%) and accuracy (76.6%) of DWI becoming significantly higher than those of PET/CT (specificity, 11.1%; p < 0.05 and accuracy, 67.2%, p < 0.05). In addition, only overall survival and progression-free survival of the two groups divided by ADC at 2.1 x 10^–3 mm²/s and SUV_max at 10 showed a significant difference (p < 0.05).

CONCLUSION. DWI may have better potential than FDG PET/CT for prediction of tumor response to therapy in NSCLC patients before chemoradiotherapy.

The national chronic obstructive pulmonary disease (COPD) audit confirms the high mortality associated with acute hypercapnic respiratory failure (AHRF) in COPD, particularly in severely acidotic patients.1 The authors highlight the observations that significant numbers of patients eligible for non-invasive ventilation (NIV) do not receive it and that NIV is almost universally the ceiling of care with only 5% of acidotic patients receiving invasive mechanical ventilation (IMV). Comparisons are made with the outcomes of clinical trials of NIV, and there is an implication that in clinical practice NIV is not being used optimally with patients being denied potentially life-saving treatment. However, patient selection is the likely explanation for the higher mortality rates in the ‘real world’. The greater mortality rates in those receiving NIV at all levels of acidosis, even after allowing for early iatrogenic acidosis due to high flow oxygen, suggests NIV is often used in patients...