Risk Of Acute Exacerbation Research Articles

534TiP - A randomized phase III study of carboplatin plus nab-paclitaxel with or without nintedanib for NSCLC with IPF (J-SONIC)

BackgroundIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by worsening dyspnea and progressive loss of lung function. Acute exacerbation of IPF is associated with high morbidity and mortality. Several studies have provided evidence of an association between lung cancer and IPF, with a prevalence of lung cancer in IPF patients ranging from 9.8% to 38%. Although the efficacy of nintedanib for IPF has been demonstrated, it has remained unknown whether this agent also reduces the risk of chemotherapy-induced acute exacerbation of IPF. Patients with interstitial pneumonia have been excluded from most prospective clinical trials for NSCLC because of the risk of acute exacerbation, with a few prospective single-arm phase II studies having been reported. In addition, it has been difficult to perform a randomized prospective clinical trial for patients with advanced NSCLC and IPF because of their rarity. Therefore, the optimal chemotherapy regimen for advanced NSCLC with IPF has thus remained unclear. Trial designChemotherapy-naïve patients with advanced NSCLC associated with IPF (enrolment target of n = 240) are randomized at a 1:1 ratio to receive four cycles of carboplatin (AUC 6 on day 1) plus nab-paclitaxel (100 mg/m2 on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg b.i.d., daily), to be followed in arm B by single-agent administration of nintedanib (150 mg b.i.d., daily). The primary end point of the study is time to acute exacerbation of IPF. Study enrolment began in May 2017 and is to continue for 3 years. Legal entity responsible for the studyIsamu Okamoto. FundingNippon Boehringer Ingelheim and Japan Agency for Medical Research and Development. DisclosureAll authors have declared no conflicts of interest.

Telomere length in COPD: Relationships with physical activity, exercise capacity, and acute exacerbations.

RationaleShorter leukocyte telomere length (LTL) is associated with reduced health-related quality of life and increased risk for acute exacerbations (AEs) and mortality in chronic obstructive pulmonary disease (COPD). Increased physical activity and exercise capacity are associated with reduced risk for AEs and death. However, the relationships between LTL and physical activity, exercise capacity, and AEs in COPD are unknown.MethodsData from 3 COPD cohorts were examined: Cohort 1 (n = 112, physical activity intervention trial), Cohorts 2 and 3 (n = 182 and 294, respectively, separate observational studies). Subjects completed a 6-minute walk test (6MWT) and provided blood for LTL assessment using real-time PCR. Physical activity was measured as average daily step count using an accelerometer or pedometer. Number of self-reported AEs was available for 1) the year prior to enrollment (Cohorts 1 and 3) and 2) prospectively after enrollment (all cohorts). Multivariate models examined associations between LTL and average daily step count, 6MWT distance, and AEs.ResultsA significant association between longer LTL and increased 6MWT distance was observed in the three combined cohorts (β = 3x10-5, p = 0.045). No association between LTL and average daily step count was observed. Shorter LTL was associated with an increased number of AEs in the year prior to enrollment (Cohorts 1 and 3 combined, β = -1.93, p = 0.04) and with prospective AEs (Cohort 3, β = -1.3388, p = 0.0003).ConclusionsAmong COPD patients, increased LTL is associated with higher exercise capacity, but not physical activity. Shorter LTL was associated with AEs in a subgroup of cohorts.

Combined pulmonary fibrosis and emphysema and idiopathic pulmonary fibrosis in non-small cell lung cancer: impact on survival and acute exacerbation

BackgroundIn non-small cell lung cancer (NSCLC) patients, concomitant idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) are independently related to poor survival. CPFE is a condition with features of both pulmonary fibrosis and emphysema. Here, we evaluated the effect of CPFE and IPF alone on the outcomes of NSCLC patients.Patients and methodsWe retrospectively evaluated 283 patients with CPFE or IPF who were diagnosed with NSCLC between November 2003 and February 2018 at two tertiary care hospitals in South Korea. Patients were classified into CPFE and IPF groups according to chest computed tomography findings.ResultsOne-hundred-and-seven patients (37.8%; mean age: 70.1 years; men 97.2%) had CPFE. Compared with IPF patients, CPFE patients had a heavier smoking history; lower diffusing capacity of carbon monoxide (78.0% vs 64.8%, p < 0.001), and lower forced expiratory volume in 1 s. Of all patients with NSCLC, 71.7% overall died during the follow-up period; 71.6% died in the CPFE group and 72.0% in the IPF group. Multivariate logistic regression analysis showed that CPFE (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.09–4.69; P = 0.029) was significantly correlated with acute exacerbations (AEs). In a Cox proportional hazards analysis, stage > III NSCLC, higher Eastern Cooperative Oncology Group performance status, and higher gender–age–physiology index score was related to higher mortality. However, CPFE was not related to a higher mortality rate in univariate (hazard ratio [HR]: 1.00; 95% CI: 0.75–1.32, P = 0.972) or multivariate analysis (HR: 0.89; 95% CI: 0.66–1.21, P = 0.466).ConclusionsAE risk, but not all-cause mortality, was higher in patients with CPFE and NSCLC than in those with IPF and NSCLC. Physicians should be aware of the exaggerated risk of AE in patients with concomitant CPFE and NSCLC.

Prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease: systematic review and critical appraisal

ObjectiveTo map and assess prognostic models for outcome prediction in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review.Data sourcesPubMed until November 2018 and hand searched references from eligible articles.Eligibility criteria...

FLARE OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE SECONDARY TO LUNG BIOPSY

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) often presents with dyspnea and a nonproductive cough. The progression and prognosis of the disease are usually determined by the ILD subtype. The most common subtype is usual interstitial pneumonia (UIP) followed by non-specific interstitial pneumonia (NSIP)[1]. For most, the disease remains sub-clinical without progression. Flares can occur, being precipitated by insult to the lungs including infection and even lung biopsy[2]. CASE PRESENTATION: A 44-year-old female with a history of non-erosive rheumatoid arthritis on methotrexate, IV drug abuse, and slowly progressive ILD presented to the hospital due to hypoxemia and worsening cough. Computed tomography (CT) of the chest demonstrated interlobular septal thickening, subpleural peripheral honeycombing and ground-glass opacities with a bibasilar and posterior predominance. Methotrexate was discontinued and the patient was started on broad spectrum antibiotics with initiation of an infectious workup. Due to her unclear etiology of lung disease and failure to improve on antibiotics, a video assisted right upper lung biopsy on day six of hospitalization was performed. The pathology showed fibrosis with honeycombing and dilatation of bronchi consistent with UIP. The patient was then started on pulse dose steroids and rituximab as her hypoxia worsened. Eleven days after biopsy the patient was emergently intubated and ultimately placed on veno-venous extracorporeal membrane oxygenation (VV-ECMO) for refractory hypoxemia. Her course was complicated by streptococcal bacteremia with septic shock, Pseudomonas ventilator associated pneumonia, superior vena cava thrombus, and severe oropharyngeal bleeding. Unfortunately, the patient was not a candidate for lung transplant due to her severity of illness and multiple infections. She was ultimately taken off of life support on day 68 of hospitalization. DISCUSSION: Acute respiratory failure of unclear etiology can be difficult to treat as management can vary drastically. The differential diagnosis in this case includes methotrexate toxicity, infection, and RA-ILD. Ultimately the patient was diagnosed with a flare of her ILD with surgical lung biopsy possibly further exacerbating the flare. Biopsy may have been avoided with her CT findings being consistent with UIP pattern. One could argue that pathology would likely show similar findings and not be contributory to changing the course of treatment. Regardless of the cause, RA-ILD flares can be difficult to manage as treatment with steroids may not be enough and rituximab can take up to 4-6 weeks before seeing clinical improvement, if at all. CONCLUSIONS: RA-ILD can atypically progress at a rapid rate. When considering open lung biopsy, it is judicious to weigh the risks versus the benefits involved. For patients with already progressive ILD, flares must be considered as one of those risks. Reference #1: Solomon JJ, Chung JH, Cosgrove GP, et al. Predictors of mortality in rheumatoid arthritis-associated interstitial lung diseases. Eur Respir J. 2016;47(2):588-96. Reference #2: Bando M, Ohno S, Hosono T, et al. Risk of acute exacerbation after video-assisted thorascopic lung biopsy for interstitial lung disease. J Bronchology Interv Pulmonol 2009;16(4):229-35. DISCLOSURES: No relevant relationships by Jessica Boehmler, source=Web Response No relevant relationships by Nathan Brewster, source=Web Response No relevant relationships by Kareem Godil, source=Web Response No relevant relationships by Breanna Goldner, source=Web Response No relevant relationships by Ethan Stern, source=Web Response

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

P2.05-09 FDG-PET for Predicting Acute Exacerbation of Interstitial Pneumonia After Lung Cancer Surgery

Acute exacerbation of interstitial pneumonia (IP) is a critical complication after lung cancer resection. Although FDG-PET is commonly used for preoperative assessment of lung cancer, its role for predicting acute exacerbation of IP after lung cancer resection is unclear. We retrospectively analyzed data of lung cancer patients that underwent surgical resection at Gunma University Hospital between 2008 and 2016. We analyzed data from patients with IP based on computed tomography findings (IP group). As control, we also analyzed data in patients with no underlying lung disease (normal group) and with emphysema (emphysema group). Patients with sufficient FDG-PET data were selected and a final of 92 patients in the IP group, 21 patients in the normal group, and 20 patients in the emphysema group were enrolled in analysis. The FDG-PET values were measured at the aorta and the basal lung. Aorta values were used for reference and we calculated the basal/aorta ratio and analyzed correlation with preoperative factors, including acute exacerbation of IP and mortality. The basal/aorta ratio was significantly higher in the IP group when compared to normal and emphysema group (both p<0.01). The incidence of acute exacerbation of IP was 10.9%, and the sensitivity and specificity of basal/aorta value for predicting acute exacerbation of IP were 70.0% and 77.2%, respectively (cutoff of basal/aorta ratio at 0.833). Patients were further classified into high basal/aorta ratio group (n=35) and low basal/aorta ratio group (n=57). The incidence of acute exacerbation of IP was significantly higher in the high basal/aorta ratio group (p=0.035). We also compared the value of basal/aorta ratio in comparison to the existing IP acute exacerbation score. Patients were divided into low score (less than 10, n=64) and high score (higher or equal to 11, n=28). The sensitivity and specificity for predicting acute exacerbation of IP was 60.0% and 82.3%, respectively, and there was no significant difference between the high and low score groups (p=0.062). The basal/aorta ratio of FDG-PET values showed a significant correlation with the incidence of postoperative acute exacerbation of IP. Since FDG-PET is commonly used for preoperative assessment of lung cancer in Japan, it may be used not only for lung cancer staging but also for surgical indication in IP patients with lung cancer by preoperatively detecting patients at high risk for acute exacerbation.

Borderline pulmonary hypertension is associated with exercise intolerance and increased risk for acute exacerbation in patients with interstitial lung disease

BackgroundPulmonary hypertension (PH) is traditionally defined as a resting mean pulmonary artery pressure (mPAP) of ≥25 mmHg, while mPAP in the range of 21 to 24 mmHg is recognized as “borderline PH.” Interstitial lung disease (ILD) is complicated by the development of PH, which is known to be linked with exercise intolerance and a poor prognosis. Even though it has recently been recommended that PH is redefined as a mPAP of > 20 mmHg, little is known about the clinical significance of borderline PH in ILD. We evaluated whether borderline PH has an impact on the exercise capacity, risk of acute exacerbation (AE), and mortality in patients with ILD.MethodsA total of 80 patients with ILD who underwent right heart catheterization (RHC) between November 2013 and October 2016 were included. The patients were divided into 3 groups according to the mPAP values: mPAP ≤20 mmHg (No-PH group; n = 56), 20 < mPAP < 25 mmHg (Bo-PH group; n = 18), and mPAP ≥25 mmHg (PH group; n = 6). The demographic, hemodynamic, spirometric, and 6-min walk test (6MWT) data of the patients were collected. In addition, the 1-year incidence of AEs and 1-year survival of the patients after the initial RHC were also evaluated.ResultsThere were no significant differences among the 3 groups in the mean age, pulmonary function parameters or the PaO2, however, 6-min walk distance was significantly lower in both the Bo-PH and PH groups (p < 0.001 for both) as compared to the No-PH group. The results of the Kaplan-Meier analysis revealed that while there was no significant difference in the 1-year survival rate among the three groups, the 1-year incidence of AEs was significantly higher in both the Bo-PH and PH groups (p < 0.001, p = 0.023, respectively) as compared to the No-PH group.ConclusionsThe current study suggested that borderline PH may be associated with poorer exercise tolerance and an increased risk of AEs in patients with ILD. Therefore, the physicians should pay close attention to the presence of even mild elevation of the mPAP at the initial evaluation in patients with ILD.

Association between F-18 fluorodeoxyglucose uptake of noncancerous lung area and acute exacerbation of interstitial pneumonia in patients with lung cancer after resection

BackgroundIdiopathic pulmonary fibrosis is defined as a specific form of progressive fibrosing interstitial pneumonia. Postoperative acute exacerbation is considered a lethal comorbidity for patients with lung cancer, particularly when it is accompanied with idiopathic pulmonary fibrosis. Thus, pretherapeutic risk stratification for acute exacerbation has been anticipated. In this study, we aimed to investigate whether the maximum standardized uptake value of F-18 fluorodeoxyglucose is useful for assessing the postoperative risk of acute exacerbation and severe respiratory adverse events in patients with lung cancer after surgical resection. MethodsA total of 822 patients with lung cancer who underwent preoperative high-resolution computed tomography, fluorodeoxyglucose-positron emission tomography/computed tomography, and pulmonary resection between July 2012 and July 2018 were assessed. Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were measured using a 3-dimensional workstation. Multivariable analyses for acute exacerbation and severe respiratory adverse events were performed using the logistic regression model. ResultsAmong all patients, 120 (14.6%) had idiopathic pulmonary fibrosis findings on high-resolution computed tomography whereas severe respiratory adverse events were observed in 35 (4.2%) patients, including those with acute exacerbation (n = 15, 1.8%). Maximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with both acute exacerbation and severe respiratory adverse events on multivariable analysis, both in all patients and in the 120 patients with idiopathic pulmonary fibrosis. Risk stratification analysis showed that 19.0% and 30.2% of patients who were positive for idiopathic pulmonary fibrosis on high-resolution computed tomography and with a maximum standardized uptake value of the main tumor and that of the noncancerous lung area 1.69 or greater (the optimal cutoff value relevant to acute exacerbation) experienced acute exacerbation and severe respiratory adverse events, respectively. ConclusionsMaximum standardized uptake value of the main tumor and that of the noncancerous lung area were independently associated with the incidence of postoperative acute exacerbation and severe respiratory adverse events in patients with lung cancer.

Tiotropium inhibits proinflammatory microparticle generation by human bronchial and endothelial cells

Tiotropium is a muscarinic antagonist that reduces the risk of acute exacerbations of chronic obstructive pulmonary disease, possibly through an as yet incompletely characterized anti-inflammatory activity. We hypothesized that muscarinic activation of bronchial epithelial cells and endothelial cells causes the release of proinflammatory microparticles and that tiotropium inhibits the phenomenon. Microparticle generation was assessed by a functional assay, by flow cytometry and by NanoSight technology. Immortalized bronchial epithelial cells (16HBE) and umbilical vein endothelial cells were treated with acetylcholine in the presence of varying concentrations of tiotropium. Intracellular calcium concentration, extracellular regulated kinase phosphorylation and chemokine content in the conditioned media were assessed by commercial kits. Acetylcholine causes microparticle generation that is completely inhibited by tiotropium (50 pM). Microparticles generated by acetylcholine-stimulated cells increase the synthesis of proinflammatory mediators in an autocrine fashion. Acetylcholine-induced upregulation of microparticle generation is inhibited by an inhibitor of extracellular regulated kinase phosphorylation and by a phospholipase C inhibitor. Tiotropium blocks both extracellular regulated kinase phosphorylation and calcium mobilization, consistent with the hypothesis that the drug prevents microparticle generation through inhibition of these critical pathways. These results might contribute to explain the effect of tiotropium in reducing acute exacerbations of chronic obstructive pulmonary disease.

A Low Lean-to-Fat Ratio Reduces the Risk of Acute Exacerbation of Chronic Obstructive Pulmonary Disease in Patients with a Normal or Low Body Mass Index.

BackgroundIncreased risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) has been reported in patients who are overweight and obese. However, the effects of body fat in patients with normal or low body mass index (BMI) and COPD remain unknown. This study aimed to examine the association between acute exacerbations of COPD and the lean-to-fat (LTF) ratio in patients with a normal or low BMI.Material/MethodsPatients with COPD (n=68) underwent assessment of body composition, in whom 43 cases had a normal BMI (18.5 to 25 kg/m2) and 14 cases were underweight (<18.5 kg/m2). Patients with COPD were treated according to current clinical guidelines and underwent regular follow-up for one year. Acute exacerbations of COPD were recorded.ResultsBMI, the fat-free mass index (FFMI), skeletal muscle mass index (SMMI), and LTF ratio had no significant effect of the risk of acute exacerbations of COPD in the whole study cohort, but a low LTF ratio was significantly associated with reduced risk of acute exacerbations of COPD in the subgroup with a BMI<25 kg/m2 (OR=4.528; P<0.05). The Fat Mass Index (FMI) had a protective effect in the whole cohort (OR=0.292; P=0.024) and in the subgroup with BMI <25 kg/m2 (OR=0.253, P=0.049). The cumulative incidence of acute exacerbations of COPD was significantly increased in the patients with a high LTF ratio in the whole cohort (P=0.047) and in the subgroup with BMI <25 kg/m2 (P=0.014).ConclusionsIn patients with BMI <25 kg/m2, the LTF ratio was positively correlated with the risk of occurrence of acute exacerbations of COPD.

The Use of Inhaled Corticosteroids to Prevent Acute Exacerbations of COPD: A Pro/Con Debate.

The use of inhaled corticosteroids (ICS) has been accepted as standard practice following early landmark studies. These demonstrated a reduction in the risk of acute exacerbations of COPD (AECOPD). However, these studies were performed at a time when other therapies were not available and now our standards of care have changed. Other data has emerged which have also raised concerns as to an increase in the incidence of pneumonia in COPD patients taking inhaled corticosteroids. It is thus timely to evaluate the evidence. We present the two sides of this debate and consider the evidence both for the use of ICS as the best therapy to reduce the risk of AECOPD and also the evidence for the use of bronchodilators as a more effective and safer alternative. It is clear that as we approach an age of personalised medicine taking a "one size fits all" approach is both intellectually and medically wrong. We present the evidence that will help clinicians make better decisions for each of their patients.

Effects of long-term macrolide therapy at low doses in stable COPD.

Background: Chronic obstructive pulmonary disease (COPD) is currently the fourth largest fatal disease in the world, and is expected to rise to third place by 2020. Frequent acute exacerbations lead to increased mortality. Some suggestions for prophylactic use of macrolides in preventing COPD exacerbations have been raised, but there are still several issues that need to be addressed, such as target population, the course of treatment, therapeutic dose, and so on.Objective: To evaluate, via exploratory meta-analysis, the efficacy of long-term macrolide therapy at low doses in stable COPD.Methods: A systematic literature search was performed in PubMed, Embase, and Cochrane database from inception to March 28, 2019. Randomized controlled trials (RCT) which reported long-term use of macrolides in prevention of COPD were eligible.Results: A total of 10 articles were included in this study. It was found that there was a 23% relative risk reduction in COPD exacerbations among patients taking macrolides compared to placebo (P<0.01). The median time to first exacerbation was effectively prolonged among patients taking macrolides vs placebo (P<0.01). Sub-group analysis showed erythromycin was advantageous and older patients were less responsive to macrolides.Conclusions: Long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD. The treatment was well tolerated, with few adverse reactions, but it was not suitable for the elderly. It is recommended that this treatment regimen could be used in patients with GOLD grading C or D, because they have a higher risk of acute exacerbation and mortality. It needs to be further discussed whether this treatment should last for 12 months or longer.

Pulmonary F-18 FDG uptake of non-tumor area in lung cancer patients to provide risk stratification in postoperative acute exacerbation of interstitial lung disease.

e13165 Background: The incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is higher than the general population. In IPF patients with lung cancer, postoperative acute exacerbation (AE) is considered a fatal comorbidity. This study aimed to investigate whether FDG-PET/CT can be used to assess the risk of postoperative AE of IPF and severe respiratory adverse events (SRAE),which are defined as grade 3a or more severe respiratory complications such as AE, bacterial pneumonia, empyema, and bronchial fistula based upon Clavian-Dindo classification. Methods: We identified 822 patients with lung cancer who had preoperative FDG-PET/CT and subsequent pulmonary resection from July 2012 to July 2018. We reviewed the patients’ clinical records and transferredthe preoperative FDG-PET/CT images of each patient to SynapseVincent system (Fujifilm Corporation, Tokyo, Japan) for measuring SUV value of the lung.Inevery case, both SUVmax of main tumor (tumor-SUVmax) and non-lung tumor part (NLT-SUVmax) were measured. Univariate and multivariate analyses were performed for exploring significant parameters associated with AE and SRAE. Results: The cohort in this study consisted of 460 men and 362 women (mean age 67.9 ± 10.1 years; range 23–87). SRAE was observed in 35 (4.2%) patients including those with AE (n = 16, 1.9%). NLT-SUVmax and presence of IPF on CT were the independent predictive factors for both AE and SRAE. The receiver operating characteristic (ROC) area under the curve (AUC) of significant factors associated with AE and SRAE was measured, and cut-off levels on ROC curves for significant parameters associated with AE and SRAE were 1.69 and 1.55, respectively. The risk rates for the incidence of AE and SRAE according to NLT-SUVmax and chest CT findings were 19.0 % and 30.2% of the patients with positive IPF on CT and NLT-SUV max ≥1.69. Conclusions: NLT-SUVmax was the independent predictor of the incidence of AE and SRAE for patients who underwent pulmonary resection. FDG/PET-CT can be used in routine clinical practice to identify high-risk individuals for AE who require careful and intensive observation after pulmonary resection and that can facilitate clinical decision-making.

Risk of acute exacerbation between acetaminophen and ibuprofen in children with asthma.

BackgroundAntipyretics are widely prescribed in pediatric practice. Some reports have mentioned that acetaminophen and non-steroid anti-inflammatory drugs may negatively affect asthma control by causing asthma exacerbation (AE). However, many confounding factors can also influence the risks. We assessed the impact of using acetaminophen or ibuprofen on AE in asthmatic children, especially those with strong risk factors.MethodsWe used the 2010 Taiwan National Health Insurance Research Database and identified 983 children with persistent asthma aged 1–5 years old; among them, 591 used acetaminophen alone and 392 used ibuprofen alone in 2010. Then, we analyzed the risk of AE over 52 weeks in the patients with and without severe AE in the previous year.ResultsThe ibuprofen group had a higher risk of an emergency room (ER) visit or hospitalization for AE (odds ratio (OR) = 2.10, 95% confidence interval (CI) [1.17–3.76], P = 0.01). Among asthmatic children who had severe AE in the previous year, the risk of AE was higher in the ibuprofen group than in the acetaminophen group (OR = 3.28, 95% CI [1.30–8.29], P = 0.01), where as among those who did not, the risks of AE were similar between the acetaminophen and ibuprofen groups (OR = 1.52, 95% CI [0.71–3.25], P = 0.28).ConclusionsAmong young asthmatic children, use of ibuprofen was associated with a higher risk of AE than acetaminophen, if they had severe AE with ER visit or hospitalization in the previous year. Pediatricians should use antipyretics among children with asthma after a full evaluation of the risk.

Differing severities of acute exacerbations of idiopathic pulmonary fibrosis (IPF): insights from the INPULSIS\xae trials

BackgroundGiven the broad definition of an acute exacerbation of IPF, it is likely that acute exacerbations are heterogeneous in their aetiology, severity and clinical course. We used pooled data from the INPULSIS® trials of nintedanib versus placebo to investigate whether acute exacerbations reported as serious adverse events were associated with higher mortality than those reported as non-serious adverse events and to assess the effect of nintedanib on these types of events.MethodsAdverse events considered by an investigator to be an acute exacerbation were adjudicated as a confirmed acute exacerbation, suspected acute exacerbation, or not an acute exacerbation. Time to first investigator-reported acute exacerbation or confirmed/suspected acute exacerbation reported as a serious adverse event or non-serious adverse event over the 52-week treatment period was assessed post-hoc. Deaths were assessed based on data collected over the 52-week treatment period.ResultsOf 63 patients who had ≥1 investigator-reported acute exacerbation, 48 (76.2%) had a first acute exacerbation reported as a serious adverse event. Thirty-six (3.4%) patients had ≥1 confirmed/suspected acute exacerbation, of whom 31 had a first event reported as a serious adverse event. Investigator-reported acute exacerbations reported as serious adverse events occurred in 23 patients in the nintedanib group and 26 in the placebo group. Confirmed/suspected acute exacerbations reported as serious adverse events occurred in 10 and 21 patients in these groups, respectively. Nintedanib significantly reduced the risk of a first acute exacerbation reported as a serious adverse event (HR 0.57 [95% CI: 0.32, 0.99]; p = 0.0476) and the risk of a first confirmed/suspected acute exacerbation reported as a serious adverse event (HR 0.30 [95% CI: 0.14, 0.64]; p = 0.0019) versus placebo. A higher proportion of patients with investigator-reported acute exacerbations reported as serious adverse events died than patients with acute exacerbations reported as non-serious adverse events (61.2% versus 7.1%).ConclusionDifferent severities of acute exacerbation of IPF may exist. Acute exacerbations reported as serious adverse events in the INPULSIS® trials were associated with high mortality. Nintedanib significantly reduced the risk of acute exacerbations reported as serious adverse events.Trial registrationClinicalTrials.govNCT01335464 and NCT01335477.

Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: a prospective study and review of the literature.

Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It's defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12-36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease.

Risk of acute exacerbations in chronic obstructive pulmonary disease associated with biomass smoke compared with tobacco smoke

BackgroundRisk of exacerbations in chronic obstructive pulmonary disease (COPD) associated with biomass smoke has not been well addressed, although biomass smoke is similar in composition to tobacco smoke.MethodsTo investigate whether the risk of exacerbations in COPD associated with biomass smoke differs from that in COPD associated with tobacco smoke, we recruited patients with COPD from two Korean multicenter prospective cohorts. In a multiple linear regression model, the standardized regression coefficient (β) of biomass smoke exposure ≥25 years was most similar to that (β′) of tobacco smoke exposure ≥10 pack-years (β = − 0.13 and β′ = − 0.14). We grouped patients with COPD into four categories based on the above cut-offs: Less Tobacco-Less Biomass, Less Tobacco-More Biomass, More Tobacco-Less Biomass, and More Tobacco-More Biomass. The main outcome was the incidence of moderate or severe exacerbations.ResultsAmong 1033 patients with COPD, 107 were included in Less Tobacco-Less Biomass (mean age: 67 years, men: 67%), 40 in Less Tobacco-More Biomass (mean age: 70 years, men: 35%), 631 in More Tobacco-Less Biomass (mean age: 68 years, men: 98%), and 255 in More Tobacco-More Biomass (mean age: 69 years, men: 97%). The incidence rates of exacerbations were not significantly different between Less Tobacco-More Biomass and More Tobacco-Less Biomass (adjusted incidence rate ratio, 1.03; 95% confidence interval, 0.56–1.89; P = 0.921). No interaction between sex and tobacco and biomass smoke was observed. When propensity score matching with available covariates including age and sex was applied, a similar result was observed.ConclusionsPatients with COPD associated with biomass smoke and those with COPD associated with tobacco smoke had a similar risk of exacerbations. This suggests that patients with COPD associated with biomass smoke should be treated actively.

Efficacy and risk of cytotoxic chemotherapy in extensive disease-small cell lung cancer patients with interstitial pneumonia

BackgroundSmall cell lung cancer (SCLC) is characterized by a high propensity for metastases and a poor prognosis irrespective of high sensitivity for initial chemotherapy. Although interstitial pneumonia (IP) is one of risk factors for lung cancer, efficacy of cytotoxic chemotherapy for patients with SCLC with IP remains unclear. Our study aims to evaluate the efficacy of systemic chemotherapy and assess risk of acute exacerbation (AE)-IP with cytotoxic drugs for extensive disease (ED)-SCLC patients with IP.MethodsWe performed a retrospective study of 192 consecutive ED-SCLC patients with IP (n = 40) and without IP (n = 152) between 2008 and 2016.Result31 of 40 ED-SCLC patients with IP and 130 of 152 patients without IP received systemic chemotherapy. The efficacy of chemotherapy in patients with IP was not inferior to that in patients without IP (overall survival [OS], 7.1 [95% confidence interval (CI): 0.2–14.0] vs. 10.0 [95% CI: 8.2–11.8] months, P = 0.57). Pretreatment serum levels of lactate dehydrogenase (LDH; 651.7 ± 481.0 vs. 301.4 ± 110.7 U/mL, P = 0.01) and C-reactive protein (CRP; 8.9 ± 9.6 vs. 1.8 ± 1.8 U/mL, P = 0.008) were correlated with developed AE-IP in the ED-SCLC patients with IP.ConclusionSystemic chemotherapy was effective even in ED-SCLC patients with IP. However, the risk of developed AE-IP that was high in patients with IP and should be evaluated using serum LDH and CRP levels before initial chemotherapy.

Adding a LAMA to ICS/LABA Therapy: A Meta-analysis of Triple Combination Therapy in COPD

Inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) combination is commonly prescribed to treat COPD; therefore, we performed a meta-analysis on the effect of adding a long-acting muscarinic receptor antagonist (LAMA) to ICS/LABA combination in COPD. Studies were identified by searching in different databases the randomized controlled trials that investigated the effect of ICS/LABA/LAMA combination in COPD. The primary end points were the effect of triple therapy on trough FEV1, risk of acute exacerbation of COPD (AECOPD), and risk of cardiovascular serious adverse events (SAEs), compared with ICS/LABA combination. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the quality of evidence. Thirteen randomized controlled trials including 15,519 patients with COPD (ICS/LABA/LAMA combination, 53.1%; ICS/LABA combination, 46.9%) were meta-analyzed. ICS/LABA/LAMA combination improved trough FEV1 (mean difference,+104.86mL; 95%CI, 86.74-122.99; high quality of evidence) and protected against AECOPD (relative risk, 0.78; 95%CI, 0.71-0.85; high quality of evidence) vsICS/LABA combination. For every approximately four patients treated with triple therapy, one increased FEV1 > 100mL, and approximately 26 patients had to be treated for 1 year with ICS/LABA/LAMA combination to prevent one AECOPD, compared with ICS/LABA combination. Adding a LAMA to ICS/LABA therapy did not modulate the risk of cardiovascular SAEs (moderate quality of evidence). Triple therapy provides significant clinical benefit in patients with COPD on ICS/LABA combination. ICS/LABA therapy can be escalated to triple therapy without a real risk to increase cardiovascular SAEs when a LAMA is added to the combination. ClinicalTrials.gov; No.: CRD42018095300; URL: www.clinicaltrials.gov.