Impact of Age and Gender on Response to Asthma Therapy.

Am J Respir Crit Care Med. 2015 Jun 11;

Authors: Dunn RM, Lehman E, Chinchilli VM, Martin RJ, Boushey HA, Israel E, Kraft M, Lazarus SC, Lemanske RF, Lugogo NL, Peters SP, Sorkness CA, Szefler S, Wechsler ME, NHLBI Asthma Clinical Research Network.

Abstract
RATIONALE: Age and gender are associated with differences in asthma prevalence and morbidity.
OBJECTIVES: Determine if age and gender associate with distinct phenotypes and a variable response to therapy in mild-moderate asthmatics.
METHODS: We utilized Asthma Clinical Research Network data to determine the impact of age and gender on phenotypes and treatment failures among subjects participating in 10 trials from 1993 to 2003.
MEASUREMENTS AND MAIN RESULTS: 1,200 subjects were identified [median age = 30.4 years, male = 520 (43.3%), female = 680(56.7%)] and analyzed. A higher proportion of subjects ≥30 years old experienced treatment failures (17.3% vs. 10.3%; OR=1.82, CI=1.30-2.54; P < 0.001); and rates increased proportionally with increasing age above 30 across the cohort [OR per year = 1.02, CI=1.01-1.04), OR per 5-year = 1.13 (CI 1.04-1.22), P<0.001]. Lower lung function and longer duration of asthma were associated with a higher risk of treatment failure. A higher proportion of subjects ≥30 years old receiving controller therapy experienced treatment failures. When stratified by specific therapy, treatment failures increased consistently for every year above age 30 in subjects on inhaled corticosteroids [OR per year = 1.03 (CI 1.01-1.07)]. Females had a slightly higher FEV1% predicted (84.5% vs. 81.1%; P <0.001) but similar asthma control measures. There was not a statistically significant difference in treatment failures between females and males (15.2% vs. 11.7%, P =0.088).
CONCLUSION: Older age is associated with an increased risk of treatment failure, particularly in subjects taking inhaled corticosteroids. There was no significant difference in treatment failures between genders.

PMID: 26068329 [PubMed - as supplied by publisher]

The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma.

Thorax. 2015 Jun 11;

Authors: Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, Denburg JA, HayGlass KT, Kobor MS, Kollmann TR, Kozyrskyj AL, Lou WY, Mandhane PJ, Miller GE, Moraes TJ, Pare PD, Scott JA, Takaro TK, Turvey SE, Duncan JM, Lefebvre DL, Sears MR, CHILD Study investigators

Abstract
The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.

PMID: 26069286 [PubMed - as supplied by publisher]

Related Articles

Aerosolized Medications for Gene and Peptide Therapy.

Respir Care. 2015 Jun;60(6):806-24

Authors: Laube BL

Abstract
Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for systemic delivery that do not cause persistent cough or changes in lung function.

PMID: 26070576 [PubMed - in process]

Related Articles

Assessing New Technologies in Aerosol Medicine: Strengths and Limitations.

Respir Care. 2015 Jun;60(6):833-49

Authors: Berlinski A

Abstract
Aerosols are the mainstay of treatment for pulmonary diseases such as asthma, cystic fibrosis, and COPD. In addition, aerosols are also being used for systemic drug delivery. Patients need devices that are safe, reliable, portable, and easy to use; have few steps in their operation; help them keep track of the remaining doses; are not expensive; and provide age-appropriate positive reinforcement and feedback. Computational fluid dynamics, human factor sciences, and quality by design are now applied to device development. Matching patient, drug, and device remains a challenge. Formulary restrictions, the current status of the industry-academia relationship, and the need to use multiple platforms hinder the process. Patients and families need to participate in the selection of a device that is appropriate for them. Practitioners need comparative data to help them choose the right device. New devices and drugs can be compared with the existing technology using in vitro and in vivo methods (lung imaging, pharmacokinetic and pharmacodynamics studies). Drug manufacturers need to be able to justify coverage of new products by third-party payers by showing a positive cost/benefit relationship. Finally, post-market surveillance is necessary for old drugs with new devices or for new drugs and devices to ensure patient safety.

PMID: 26070578 [PubMed - in process]