The first drug specific for cystic fibrosis (CF) was approved in 1993, and since then several other drugs have been approved. Median predicted survival in people with CF has improved from approximately 30 years to 44.4 years over that same period. In 2020, highly-effective modulators of the cystic fibrosis transmembrane conductance regulator became available to approximately 90% of people with CF ages 12 years and older. These transformative therapies will surely reduce morbidity and further extend longevity. The drug development pipeline is filled with therapies that address most aspects of CF disease. As survival and CF therapies have advanced, and the complexity of CF care increases, the process of drug development has become more sophisticated. In addition, detecting meaningful changes in clinical outcomes has become more difficult as the health status of people with CF improves. Design of clinical trials in CF has become more complex, and innovative approaches are required to continue to advance drug development. This review provides a general overview of drug development from the pre-clinical phase through Phase IV. Special considerations with respect to CF are integrated into the discussion of each phase of drug development. The dawn of a new era has arrived for people with CF. As CF care evolves, drug development must continue to evolve as well, until a one-time cure is available to all people with CF.
RATIONALE: Outpatient treatment of lower respiratory tract infection (LRTI) in tracheostomy dependent children varies institutionally. The objective of this study was to identify whether only increasing airway clearance (AWC) increased the odds of hospitalization within 28 days of treatment. Our hypothesis was that those treated with antibiotics were less likely to be hospitalized. METHODS: We retrospectively reviewed medical charts of children who were tracheostomy dependent between 2012-2019 and followed at our institution. We recorded recommendations with each sick call, i.e. prescription of antibiotics and/or increase in frequency of airway clearance. Generalized estimating equation models were used to determine whether the recommendation to increase AWC frequency was associated with an increased risk of hospitalization within 4 weeks, as compared to the prescription of oral and/or inhaled antibiotics. RESULTS: Of the eighty -two patients reviewed, there were 283 unique episodes of LRTI. 160 (45%) episodes involved increasing AWC alone and 195 (55%) were given an antibiotic in addition to increasing AWC. Of those who received AWC only, 21.7% were hospitalized within 28 days of treatment, and 13.8% were hospitalized after treatment with increased AWC and oral/inhaled antibiotics, p= 0.08. Those who received only AWC did not have significantly higher odds of hospitalization within 28 days of treatment, compared to those who received an antibiotic: adjusted OR 1.47 (95% CI: 0.75, 2.86); p=.26. CONCLUSIONS: In this retrospective cohort study of pediatric patients with tracheostomy, a recommendation to increase airway clearance only versus initiating an antibiotic was not associated with increased odds of hospitalization.