Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

Genetic segregation of airway disease traits despite redundancy of calcium-activated chloride channel family members.

Complex airway diseases such as asthma and chronic obstructive pulmonary disease exhibit stereotyped traits (especially airway hyperreactivity and mucous cell metaplasia) that are variably expressed in each patient. Here, we used a mouse model for virus-induced long-term expression of these traits to determine whether individual traits can be genetically segregated and thereby linked to separate determinants. We showed that an F2 intercross population derived from susceptible and nonsusceptible mouse strains can manifest individual phenotypic extremes that exhibit one or the other disease trait. Functional genomic analysis of these extremes further indicated that a member of the calcium-activated chloride channel (CLCA) gene family designated mClca3 was inducible with mucous cell metaplasia but not airway hyperreactivity. In confirmation of this finding, we found that mClca3 gene transfer to mouse airway epithelium was sufficient to induce mucous cell metaplasia but not airway hyperreactivity. However, newly developed mClca3(-/-) mice exhibited the same degree of mucous cell metaplasia and airway hyperreactivity as wild-type mice. Bioinformatic analysis of the Clca locus led to the identification of mClca5, and gene transfer indicated that mClca5 also selectively drives mucous cell metaplasia. Thus, in addition to the capacity of CLCA family members to exhibit diverse functional activities, there is also preserved function so that more than one family member mediates mucous cell metaplasia. Nonetheless, Clca expression appears to be a selective determinant of mucous cell metaplasia so that shared homologies between CLCA family members may still represent a useful target for focused therapeutic intervention in hypersecretory airway disease.

Comparing the utility of a standard pediatric resuscitation cart with a pediatric resuscitation cart based on the Broselow tape: a randomized, controlled, crossover trial involving simulated resuscitation scenarios.

BACKGROUND: Access to resuscitation equipment is a critical component in delivering optimal care in pediatric arrest situations. Historically, children's hospitals and clinics have used a standard pediatric resuscitation cart ("standard cart") in which drawers are organized by intervention (eg, intubation module, intravenous module), requiring multiple drawers to be opened during a code. Many emergency departments, however, use a pediatric resuscitation cart based on the Broselow tape ("Broselow cart") in which each drawer is color coded and organized by patient length and weight ranges; each drawer contains all necessary equipment for resuscitation of a patient in that specific length/weight range. A literature review has revealed no studies examining the utility of either cart. OBJECTIVES: To compare which resuscitation cart organization (standard versus Broselow) allows for faster access to equipment, more accurate selection of appropriately sized equipment, and better user satisfaction. Methodology. We performed a prospective, randomized, controlled, crossover trial in which 21 pediatric health care providers were assigned the role of obtaining the appropriate equipment during 2 standardized, simulated codes alternately using either a standard or Broselow cart. Time to and accuracy of the selection of appropriate medical equipment along with posttesting satisfaction were measured. All simulations were performed in the Center for Advanced Pediatric Education at Stanford University Medical Center (Stanford, CA), a training facility designed to replicate the real medical environment with the technology to allow for videotaping of scenarios. RESULTS: Of the 21 subjects, 62% found the Broselow cart "easy" or "very easy" to use versus 33% for the standard cart. Of the 21 subjects, 67% preferred the Broselow cart, 10% preferred the standard cart, and 23% indicated no preference. Intubation supplies and nasogastric tubes were found significantly faster when using the Broselow cart (mean time: 29.1 and 20 seconds, respectively) versus the standard cart (mean time: 38.7 and 38.2 seconds, respectively). Correct equipment was provided a statistically significant 99% of the time with the Broselow cart versus 83% of the time with the standard cart. Ten percent of the subjects had prior experience with the Broselow cart versus 62% having experience with the standard cart. CONCLUSIONS: Despite less prior experience with the Broselow cart, subjects in this study found it easier to use and preferred it over the standard cart. In addition, subjects located intubation equipment and nasogastric tubes significantly faster when using the Broselow cart, and correct equipment was provided significantly more often with the Broselow cart. These data suggest that sites caring for pediatric patients should consider modeling their resuscitation carts after the Broselow cart to enhance provider confidence and patient safety.