Acute exacerbation predicting poor outcomes in idiopathic interstitial pneumonia and advanced lung cancer patients undergoing cytotoxic chemotherapy
Atsushi MiyamotoHirofumi MichimaeYasuharu NakaharaShinobu AkagawaKazuhiko NakagawaYuji MinegishiTakashi OguraShigeto HontsuHiroshi DateKazuhisa TakahashiSakae HommaKazuma KishiYoshio NakaharaKen OhtaAkihiko GemmaYasuo NishizakaTakashi OguraHiromichi KimuraKoji NishiMakoto NakamuraKoshi YokomuraH. TaniguchiKeisuke TomiiJ ShindoKeita SatoY TaguchiHiroki TakahashiH. TakizawaSakae HommaShôji NakamuraKosuke YoshimuraKazuhiro UsuiKazuya IchikadoA. BessyoHaruo SugiyamaYoshinori HasegawaHiroyuki NakamuraHiroshi SagaraKenji UbeFumie NomuraKatsuyuki KiuraFumiaki YoshiikeKazuhisa TakahashiT KitaHitomi SakaiMasashi BandoTakeshi MatsumotoTakuya InoueTakashi KijimaHiroshi MukaeN. MasudaN. MatsumotoFumio SakamakiM. KamimuraAtsushi TakiseTomoo KishabaYasuhiko NishiokaKosuke KashiwabaraAsako YamamotoS. FujiuchiMasato ShingyojiMasayuki HanaokaShigeru TominagaJun‐ichi KadotaTakaoki KasaharaMitsuo MotegiT. HaradaS. IshikawaT. SudaY TomizawaRyusuke HayashiMasahiro ShinodaMitsuo TeradaY. JinYusuke ShikamaTetsuro KikuchiKenji KidoAkira YokoyamaS. FukeH. NagaseHirotaka TanakaN. HizawaKana MiyazakiSatoshi IkushimaNaoki SakaiTomoaki HoshinoM. MishimaHiroshi OhnishiHideo ImaiS. NagashimaEiji KojimaShuji Oh‐ishiYuichiro OheShin‐ichiro IwakamiM. MineshitaY. KomaseHiroshi HaradaShiro ImokawaH. WatanabeMasao IchikiKazuyoshi KuwanoNorihiko TakahashiNaohiko ChonabayashiTomoka HisadaMasahiro YoshidaKeiichiro HirataKeiko WatanabeYukio SuginoShinichiro YoshiokaHideo TomiokaMasaru AoshimaYuji SugimotoMasumi IchinoseS. TamakiMasami TsuchiyaHiroshi KatayamaYasuhiko OkochiHirotaka TanakaK. OgataTakahiro TsuburaiI. Honda
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Abstract Effective treatment for advanced lung cancer and idiopathic interstitial pneumonia (IIP) remains an unmet medical need. The relationship between chemotherapy’s effectiveness in advanced lung cancer and the risk of acute exacerbation of IIP is poorly investigated. There is limited evidence that patients who experience an acute exacerbation of IIPs during cytotoxic chemotherapy have poorer outcomes than those who do not. Among 1004 patients with advanced lung cancer and IIPs enrolled in our published multi-centre retrospective study from 110 Japanese institutions, 708 patients (male: female, 645:63; mean age, 70.4) received first-line chemotherapy. The occurrence of chemotherapy-triggered acute exacerbations of IIPs and overall survival (OS) were analysed. The OS between groups of patients with and without the occurrence of acute exacerbation was compared at four landmark time points (30, 60, 90, and 120 days), starting from the first-line chemotherapy, using the landmark method. The incidence of acute exacerbation in patients who received first-line chemotherapy with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) was more frequent in NSCLC patients than in SCLC (4.2% vs 12.6%; odds ratio [OR]: 3.316; 95% confidence interval [CI] 1.25–8.8). Median survival time was 9.9 months (95% CI 9.2–10.7). Patients who experienced acute exacerbation had significant worse survival outcomes than those who did not at various time points (30 days, hazard ratio [HR]: 5.191, 95% CI 2.889–9.328; 60 days, HR: 2.351, 95% CI 1.104–5.009; 90 days, HR: 2.416, 95% CI 1.232–4.739; and 120 days, HR: 2.521, 95% CI 1.357–4.681). Acute exacerbation during first-line chemotherapy can predict poor survival. Trial Registration number: UMIN000018227.Abstract Background: At present, there is little information in Bulgaria regarding the rate and stability of frequent-exacerbation phenotype in COPD patients. Aim: To study the rate and stability of frequent-exacerbation phenotype in COPD patients. Materials and methods: We followed up 465 COPD patients for exacerbations over a 3-year period. Exacerbations were defined as events that resulted in treatment with antibiotics and/or corticosteroids (moderate), or that led to hospitalization (severe). Result: Approximately 10% of the patients had two or more exacerbations per year (frequent-exacerbation phenotype), and this structure stayed stable over the study period. The exacerbation rate in the first year of follow up was 0.33 per stage I COPD patients (according to GOLD stages), 0.49 per stage II COPD patients; 0.69 - for stage III, and 1.06 for stage IV COPD patients. The frequent-exacerbation rate increased from stage I to stage IV by 4.35%, 9.17%, 10.79%, and 20.97%, respectively. A history of previous year exacerbations increased the risk of new exacerbations: with a history of one exacerbation - OR 2.1820 (95% CI: 1.4018 to 3.3965, p = 0.0005), and with a history of two exacerbations - OR 4.6460 (95% CI: 2.3286 to 9.2696; p < 0.0001). The frequent-exacerbation phenotype appeared to be unstable over the study period - up to 33% from those patients stayed in the phenotype for the next year. Conclusions: The exacerbation frequency and the rate of frequent-exacerbation phenotype increases with COPD progression. History of exacerbations in the previous year is a significant risk factor for exacerbations of COPD. The frequent-exacerbation phenotype appeared to be unstable over the study period. The pheno-type of non-exacerbators was more likely to remain stable over time.
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Interferon-β (IFN-β) is an effective drug in multiple sclerosis (MS) but it may cause acute exacerbation of MS following the initiation of treatment. This study evaluated patients with rapid exacerbation of multiple sclerosis (REMS) following the initiation of IFN-β.We retrospectively reviewed the clinical records of 2350 patients with multiple sclerosis who started treatment with IFN-β and were registered with Isfahan MS Society (IMSS). Patients with rapid exacerbation of multiple sclerosis within 24 hours after initiation of IFN-β treatment were selected and their demographic and clinical data were extracted.We identified nine patients with rapid exacerbation of multiple sclerosis following the initiation of IFN-β. Their mean age at the time of treatment with IFN-β was 37.3 ± 6.28 years. Seven patients had rapid exacerbation of multiple sclerosis after initiation of IFN-β 1a and two patients after IFN-β 1b. The course of disease in all of these patients was relapsing-remitting. However, all had converted into secondary progression within the first year after occurrence of rapid exacerbation of multiple sclerosis following the initiation of IFN-β.This study may indicate that the effects of IFN-β are not purely anti-inflammatory and a small percentage of MS patients experience rapid exacerbation of multiple sclerosis following the initiation of IFN-β. Future studies are needed to validate our findings.
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To determine whether an increase in plasma concentration of S-100 protein can serve as a marker for acute exacerbation of multiple sclerosis.The plasma level of S-100 protein was investigated in 28 patients suffering from multiple sclerosis. Of these, 17 patients were admitted for acute exacerbation and 11 patients had a stable disease with no clinical signs for acute exacerbation. S-100 protein concentrations in plasma were determined with an immunofluorometric sandwich assay.Plasma concentrations were significantly elevated in patients who were examined within 7 days after the onset of acute exacerbation (n = 6). S-100 levels of patients 8 to 28 days after the onset of acute exacerbation (n = 11) did not differ from healthy controls (n = 120). Eleven patients with multiple sclerosis without acute exacerbation had moderately elevated plasma levels.The plasma concentration of S-100 protein is a sensitive although unspecific indicator of neuronal damage and may be of use as a marker of disease activity in multiple sclerosis.
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Introduction and Objectives
Exacerbations in COPD significantly affect quality of life and mortality. Predicting which patients are likely to exacerbate most frequently could provide opportunities to introduce treatment strategies to reduce future exacerbations. To determine whether established exacerbation risk factors can predict future exacerbation frequency and to assess the severity of an exacerbation risk factor on exacerbation outcomes.Methods
From the literature we identified risk factors associated with COPD exacerbations and categorised these into 'moderate' and 'severe'. We identified all patients who presented with a severe exacerbation of COPD to our unit from 01 January 2018 to 31 December 2018 and recorded their number of exacerbations over 18 months. Patients were divided into 8 groups based on exacerbation frequency. Standard statistical methods were applied.Results
A total of 213 patients were studied. Across all 8 patient groups there is a positive association between number of exacerbation risk factors and exacerbation frequency. The highest exacerbation frequency group has on average 5.0 severe risk factors compared to 2.3 severe risk factors for the lowest frequency group (p<0.001), and 2.7 moderate risk factors compared to 1.8 moderate risk factors for the lowest frequency group (p<0.05).Conclusions
The study demonstrates that it is possible to predict future exacerbation frequency amongst patients with COPD. Identifying which patients are at most risk of exacerbations may help clinicians to introduce pre-emptive individualised treatment strategies to reduce future exacerbation frequency.Copd exacerbation
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Background:Exacerbations are a major contributor to the large burden of treating chronic obstructive pulmonary disease (COPD). Estimates of exacerbation costs in the United States are limited.Objective:To estimate incremental costs associated with COPD exacerbation, particularly severe exacerbation, in the United States.Methods:COPD patients with at least one exacerbation were identified in the Thomson Reuters MarketScan administrative claims database. A COPD exacerbation was defined as patient use of oral or parenteral corticosteroids on the same day or within 7 days following a claim with a COPD diagnosis. Severe exacerbation was further defined if the exacerbation was associated with hospitalization or death. Healthcare costs and exacerbations were evaluated at quarterly intervals starting from patients' first observed claim with COPD diagnostic code in the database. Incremental costs associated with exacerbation were estimated as cost differences between quarters with exacerbation and quarters without exacerbation.Results:A total of 2644,174 patient-quarters, derived from 228,978 COPD patients, were included in the analysis. The average patient was followed an average of 2.9 years. The mean total cost was $17,016 per patient-quarter with severe exacerbation, $6628 per patient-quarter with non-severe exacerbation, an average of $8726 per patient-quarters with any exacerbation compared to $4762 per patient-quarter with no exacerbation. After adjusting for patient demographics, the mean incremental total cost was $11,261 per patient-quarter with severe exacerbation, $1509 per patient-quarter for non-severe exacerbation, and $3439 per patient-quarter with any exacerbation compared with patient-quarters with no exacerbation.Limitations:The method used for defining exacerbations does not capture mild exacerbations. Additional limitations exist due to the nature of claims data.Conclusions:Exacerbations, especially severe ones, result in a significant economic burden for third-party payers. Effective management of COPD and prevention of exacerbations may lead to improved patient outcomes and reduction in total healthcare costs for long-term management of COPD.
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Abstract COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman’s rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was −0.71 ( p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak ( r = −0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers ( β = −5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total ( r = 0.22, p < 0.05), Mastery ( r = 0.22, p < 0.05), and Fatigue ( r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.
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Higher exacerbation incidence rates in chronic obstructive pulmonary disease (COPD) are associated with more rapid decline in lung function and poorer quality of life, yet the mechanisms determining susceptibility to exacerbation remain ill-defined. The same viruses responsible for common colds are frequently isolated during exacerbations. The current authors hypothesised that exacerbation frequency may be associated with an increased frequency of colds, and investigated whether increased exacerbation frequency was associated with increased acquisition of colds, or a greater likelihood of exacerbation once a cold has been acquired. A total of 150 patients with COPD completed diary cards recording peak expiratory flow, and respiratory and coryzal symptoms for a median 1,047 days. Annual cold and exacerbation incidence rates (cold and exacerbation frequency) were calculated, and the relationships between these variables were investigated. This analysis is based on 1,005 colds and 1,493 exacerbations. Frequent exacerbators ( i.e. those whose exacerbation frequency was greater than the median) experienced significantly more colds than infrequent exacerbators (1.73 versus 0.94·yr −1 ). The likelihood of exacerbation during a cold was unaffected by exacerbation frequency. Patients experiencing frequent colds had a significantly higher exposure to cigarette smoke (46 versus 33 pack-yrs). Exacerbation frequency in chronic obstructive pulmonary disease is associated with an increased frequency of acquiring the common cold, rather than an increased propensity to exacerbation once a cold has been acquired.
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