Assessment of Consistency of Fixed Airflow Obstruction Status during Budesonide/Formoterol Treatment and Its Effects on Treatment Outcomes in Patients with Asthma.

BACKGROUND: The consistency of fixed airflow limitation status during treatment in patients with asthma is unknown. OBJECTIVE: The objective of this study was to determine the consistency of fixed airflow obstruction (FAO) status during treatment and effects on treatment response. METHODS: This post hoc analysis from a 12-week study (NCT00652002) assessed patients aged 12 years or more with moderate-to-severe asthma randomized to twice-daily budesonide/formoterol (BUD/FM) via pressurized metered-dose inhaler (pMDI) 320/9 µg, BUD pMDI 320 µg, FM 9 µg via dry-powder inhaler, or placebo. FAO status was assessed postbronchodilator at screening and after study drug administration at weeks 2, 6, and 12 via the forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) ratio < lower limit of normal (LLN) (FAO+) or ≥ LLN (FAO-). Patients with persistent FAO- and FAO+ retained their screening FAO status at all visits. Patients with inconsistent FAO changed categories at least once during the study. Assessments included early withdrawal due to predefined worsening asthma events (PAEs), lung function, and symptoms. RESULTS: Of 386 patients, 29% had persistent FAO+, 31% inconsistent FAO, and 40% persistent FAO-. PAEs were lowest in the FAO- group overall and with BUD/FM treatment in patients with FAO+ and inconsistent FAO. Baseline demographics and treatment responses of the inconsistent FAO group were most similar to the FAO+ group. The greatest improvements in asthma control days and use of rescue medications were seen with BUD/FM treatment, regardless of FAO status. CONCLUSIONS: Approximately one third of patients with moderate-to-severe asthma in this study had inconsistent FAO, and their treatment responses were most similar to patients with FAO+. Regardless of FAO status, patients treated with BUD/FM experienced the most improved treatment responses and fewest withdrawals due to PAEs.

Biochemical and cellular mechanisms of aging and degenerative disease: excessive, poor-quality caloric intake may deplete essential nutrients and interfere with cellular processes to produce degenerative damage.

It has long been known that caloric restriction retards aging and many degenerative disease processes. Various experiments have confirmed that caloric restriction enables animals' organelles and cells to retain their structural integrity into old age, in contrast to ad libitum counterparts. Calorically restricted animals also maintain greatly enhanced immune and DNA repair systems, handle outside threats-infectious agents, toxins, radiation, extreme temperatures-more proficiently, and usually avoid or defer the onset of cancers. But how caloric restriction works to achieve these remarkable results has so far eluded us. Our hypothesis suggests that the key to understanding how caloric and nutrient levels can influence so many physiological functions is to perceive food intake not only as a means of nourishing and strengthening the organism, but also as an environmental challenge. The organism's biochemical responses to excessive, particularly poor-quality, calorie intake, like its responses to other environmental threats, can potentially deplete essential nutrients, interfere with biochemical and cellular mechanisms, and produce degenerative damage. This chain of events occurs not only in animals in caloric restriction experiments, but also in virtually all organisms as they respond to chronic or high-level environmental challenges or receive inadequate nutrition. Because they cannot avoid these challenges, consume precise levels of nutrients required to deal with ongoing metabolic functions and outside threats, and do not function physiologically with total efficiency, all organisms incur degenerative damage, essentially every day, promoting aging and leading to various degenerative disorders.