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Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint.

Lancet Oncol. 2014 Jan;15(1):e42-50

Authors: Hellmann MD, Chaft JE, William WN, Rusch V, Pisters KM, Kalhor N, Pataer A, Travis WD, Swisher SG, Kris MG, University of Texas MD Anderson Lung Cancer Collaborative Group

Abstract
Improvements in outcomes for patients with resectable lung cancers have plateaued. Clinical trials of resectable non-small-cell lung cancers with overall survival as the primary endpoint require a decade or longer to complete, are expensive, and limit innovation. A surrogate for survival, such as pathological response to neoadjuvant chemotherapy, has the potential to improve the efficiency of trials and expedite advances. 10% or less residual viable tumour after neoadjuvant chemotherapy, termed here major pathological response, meets criteria for a surrogate; major pathological response strongly associates with improved survival, is reflective of treatment effect, and captures the magnitude of the treatment benefit on survival. We support the incorporation of major pathological response as a surrogate endpoint for survival in future neoadjuvant trials of resectable lung cancers. Additional prospective studies are needed to confirm the validity and reproducibility of major pathological response within individual histological and molecular subgroups and with new drugs.

PMID: 24384493 [PubMed - indexed for MEDLINE]

Humidifier disinfectant-associated children's interstitial lung disease.

Am J Respir Crit Care Med. 2014 Jan 1;189(1):48-56

Authors: Kim KW, Ahn K, Yang HJ, Lee S, Park JD, Kim WK, Kim JT, Kim HH, Rha YH, Park YM, Sohn MH, Oh JW, Lee HR, Lim DH, Choung JT, Han MY, Lee E, Kim HY, Seo JH, Kim BJ, Cho YA, Do KH, Kim SA, Jang SJ, Lee MS, Kim HJ, Kwon GY, Park JH, Gwack J, Youn SK, Kwon JW, Jun BY, Pyun BY, Hong SJ

Abstract
RATIONALE: Beginning in 2006, epidemics of a fatal lung injury of unknown cause in children were observed in Korea every spring. A recent study demonstrated that this type of children's interstitial lung disease (chILD) is associated with humidifier disinfectant use.
OBJECTIVES: To determine the clinical characteristics of this type of chILD and to assess whether the nationwide suspension of humidifier disinfectant sales in the autumn of 2011 affected its incidence.
METHODS: The clinical characteristics of suspected cases between 2006 and 2011 were determined by a nationwide retrospective study. The potential causal relationship with humidifier disinfectants was examined by a prospective surveillance study after humidifier disinfectant sales were suspended.
MEASUREMENTS AND MAIN RESULTS: In total, 138 children were diagnosed with this type of chILD, which was characterized by rapid progression, high mortality, predominance in the spring season, and a familial tendency. The annual incidence increased in 2011 and then dropped to zero in 2012. The children were on average 30.4 months old. The most frequent symptoms at admission were cough and dyspnea. As the disease progressed, the typical complication was spontaneous air leak. Eighty children (58%) died. Two years after humidifier disinfectant-sale suspension, no more new cases were found.
CONCLUSIONS: This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

PMID: 24199596 [PubMed - indexed for MEDLINE]

Risk factors and comorbidities in the preclinical stages of chronic obstructive pulmonary disease.

Am J Respir Crit Care Med. 2014 Jan 1;189(1):30-8

Authors: Van Remoortel H, Hornikx M, Langer D, Burtin C, Everaerts S, Verhamme P, Boonen S, Gosselink R, Decramer M, Troosters T, Janssens W

Abstract
RATIONALE: There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD).
OBJECTIVES: This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening.
METHODS: Sixty subjects with preclinical COPD (63 ± 6 yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 ± 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 ± 6 yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively.
MEASUREMENTS AND MAIN RESULTS: The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities.
CONCLUSIONS: Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT 01314807).

PMID: 24219412 [PubMed - indexed for MEDLINE]

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Risk stratification for cardiac complications in patients hospitalized for community-acquired pneumonia.

Mayo Clin Proc. 2014 Jan;89(1):60-8

Authors: Corrales-Medina VF, Taljaard M, Fine MJ, Dwivedi G, Perry JJ, Musher DM, Chirinos JA

Abstract
OBJECTIVE: To derive and validate a clinical rule that stratifies the risk of cardiac complications in patients hospitalized for community-acquired pneumonia (CAP) and compare its performance to the pneumonia severity index (PSI) score.
PATIENTS AND METHODS: Two cohorts of patients hospitalized for CAP were selected for the study. We used regression techniques in the derivation cohort (1343 patients enrolled in the Pneumonia Patient Outcomes Research Team study between October 1991 and March 1994) to generate a prediction rule that we validated in the validation cohort (608 patients enrolled in the Dissemination of Guidelines for Length of Stay study between February 1998 and March 1999). Discrimination and reclassification analyses compared its performance against the PSI score.
RESULTS: A prediction model for cardiac complications in the derivation cohort included age, 3 preexisting conditions, 2 vital signs, and 7 common laboratory or radiographic parameters. Discrimination (C statistic, 0.81; 95% CI, 0.78-0.84) and calibration (Hosmer-Lemeshow goodness-of-fit test, χ(2)=13.0; P=.11) were good. We derived a point score system from this model that when applied to the validation cohort also had good discrimination (C statistic, 0.78; 95% CI, 0.74-0.83) and calibration (Hosmer-Lemeshow, χ(2)=9.0; P=.34). On the basis of this score, we defined 4 categories of incremental risk of cardiac complications. The incidence of cardiac complications across risk categories increased linearly (from lowest to highest) in both the derivation (3.0%, 17.8%, 35.2%, and 72.2%) and validation (5.0%, 8.2%, 28.3%, and 48.9%) cohorts (Cochran-Armitage linear trend test, P<.01). The new score outperformed the PSI score in predicting cardiac complications in the validation cohort (C statistic, 0.78 vs 0.74; P=.03; proportion of patients correctly reclassified by the new score, 44%).
CONCLUSION: We derived and validated a clinical rule that accurately stratifies the risk of cardiac complications in patients hospitalized for CAP.

PMID: 24388023 [PubMed - indexed for MEDLINE]