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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Aggressive Treatment Strategies in the Fight Against Cystic Fibrosis

To provide pediatric pulmonologists, pulmonologists, geneticists, and primary care physicians with up-to-date information on the diagnosis and treatment of cystic fibrosis.

This activity is designed for pediatric pulmonologists, pulmonologists, geneticists, and primary care physicians. No prerequisites required.

At the conclusion of this activity, the participant should be able to:

  • Explain the pathophysiology of cystic fibrosis (CF).
  • Identify the multiple complications in patients with CF that need to be managed in order to improve quality of life and increase survival.
  • Discuss the importance of early and aggressive therapies in preventing complications and permanent changes in lung function.
  • Recognize that preserving lung function will improve survival of patients with CF.
  • Recognize that compliance is critically important to outcomes in patients with CF.
  • Describe the relationship between nutritional status and lung function in patients with CF.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of The Johns Hopkins University School of Medicine.

The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The estimated time to complete this educational activity: 2 hours.

After reading this monograph, participants may receive credit by completing the CME test, evaluation, and receiving a score of 70% or higher.

Release date: December 15, 2007. Expiration date: December 15, 2009.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Novartis Pharmaceuticals Corporation.

Full Disclosure Policy Affecting CE Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:


Peter J. Mogayzel Jr, MD, PhD
Associate Professor of Pediatrics
Director, Cystic Fibrosis Center
Eudowood Division of Pediatric Respiratory Sciences
The Johns Hopkins Hospital
Baltimore, Maryland
Dr Mogayzel reports receiving grants/research support from Cystic Fibrosis Foundation and Inspire; and reports receiving honoraria from Cystic Fibrosis Foundation.


John Paul Clancy, MD
Professor, Director, and Raymond K. Lyrene Chair in Pediatric Pulmonology
The Children’s Hospital of Alabama and University of Alabama at Birmingham
Birmingham, Alabama
Dr Clancy reports receiving grants/research support from Gilead, Inspire, PTC Therapeutics, and Transave; serving as a consultant for Cystic Fibrosis Foundation Therapeutics; and receiving honoraria from Cystic Fibrosis Foundation and National Institutes of Health (Rare Disease Network DSMB).

Richard B. Moss, MD
Professor of Pediatrics
Divisions of Allergy and Pulmonary Medicine
Center for Excellence in Pulmonary Biology
Stanford University Medical Center
Palo Alto, California
Dr Moss reports receiving grants/research support from Inspire, PTC Therapeutics, and Vertex; serving as a consultant for Altana Pharma, Aridis Pharmaceuticals, Arriva Pharmaceuticals, Johnson & Johnson, KaloBios, Lantibio, Mpex Pharmaceuticals, Novartis, and Vertex; being a stock shareholder in Genentech and Gilead; receiving honoraria from Genentech and Novartis; and receiving other financial or material support from Cystic Fibrosis Foundation and National Institutes of Health.

Notice: The audience is advised that articles in this CME activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Moss—aztreonam, denufosol, dornase alpha, and tobramycin.

All other faculty have indicated that they have not referenced unlabeled or unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

Aggressive Treatment Strategies in the Fight Against Cystic Fibrosis
Peter J. Mogayzel Jr, MD, PhD,*

In 1938, Dr Dorothy Andersen, a New York pathologist, published a paper in which she described a new clinical entity, cystic fibrosis (CF), which was distinct from celiac disease and characterized by neonatal respiratory and intestinal complications among others, including malabsorption and characteristic pancreatic pathology.1 In the nearly 70 years since that historic publication, life expectancy for children with CF has increased dramatically. Babies once not expected to survive to their first birthday are now surviving into adulthood. In 2006, the Cystic Fibrosis Foundation reported that the mean age for survival was 36.9 years, up from a mean age of 32 only 5 years earlier, and that almost half of individuals living with CF are older than 18 years of age.2 These significant strides in longevity may be attributed to scientific advancements in the fields of genetics and medicine that have helped to identify the underlying cause of CF and contribute toward more aggressive management with an ever-expanding repertoire of treatment options. In 1955, the Cystic Fibrosis Foundation was founded, and this organization was in large part responsible for funding of research and the establishment of specialized care centers that have driven this movement toward early, aggressive, and standardized care based on evidence and best practices. Today, many patients with CF attend accredited CF centers where they receive care from a multidisciplinary team of experts in the diagnosis and treatment of CF, in addition to professionals who specialize in helping patients and families to cope with lifestyle issues and the stressors of this chronic illness.

Although recognized as an autosomal recessive genetic disorder since the 1940s, the specific gene responsible for CF was not discovered until 1989.3 Located on chromosome 7 and known to have over 1500 possible mutations, the cystic fibrosis transmembrane conductance regulator (CFTR) gene is now known to cause defects in chloride transport accompanied by increased sodium reabsorption and reduced water content in secretions, thus increasing their viscosity. Before the discovery in 1953 of abnormalities in sweat that led to the pivotal development of diagnostic testing for sweat chloride concentration to confirm the presence of CF, it was widely held that CF was a defect in mucus because of the observation that patients with CF had thick, tenacious mucus.1 CFTR abnormalities cause damage to epithelial cells in exocrine glands, produce thickened secretions (including viscous mucus), and resultant obstructions or other damage to affected organs and associated structures, such as the sweat ducts, lungs, gastrointestinal tract (pancreas, intestines, and hepatobiliary tree), and reproductive organs.

In the days before current diagnostic testing was available, clinicians relied on clinical features to identify CF. These are still important today because there are some individuals with CF who have normal or only slightly elevated sweat chloride concentrations. However, scientists have also developed other diagnostic parameters, including CFTR mutation analysis and nasal transepithelial potential difference to diagnose patients with CF. Assessment of intestinal, liver, and/or gall bladder function, semen analysis, identification of pansinusitis, and tests that monitor lung function are also used in the evaluation of patients with atypical forms of CF. Prenatal and neonatal testing techniques have also been perfected and are in widespread use.

The major source of morbidity and mortality for individuals with CF is pulmonary disease, although it has been observed that the lungs are essentially normal at birth. However, babies born with CF very rapidly develop chronic bacterial infections with difficult-to-treat pathogens, such as Pseudomonas aeruginosa. Infection leads to an inappropriately strong and prolonged immune response that sets up a vicious cycle of inflammation and infection perhaps initiated by the damaged chloride channels that make them easier to attract and slower to clear bacteria.1 Bronchiectasis is a serious cause of pulmonary morbidity and mortality among patients with CF, and treatment is aimed at arresting the progression of lung damage before it has reached this stage. However, airway damage is not the only significant issue for those suffering from CF. Eighty-five percent of patients with CF have pancreatic insufficiency that leads to malabsorption of proteins and fats (including fat-soluble vitamins) and a large proportion of patients go on to develop CF-related diabetes. Other life threatening—albeit rare—gastrointestinal pathology includes severe obstructive biliary cirrhosis. End-stage liver or lung disease may result in the urgent need for organ transplantation, which poses challenges and risks while not offering a cure.

Forty years ago, clinicians described a detailed method of management laying the foundations of modern treatment that included early diagnosis, nutritional therapy to reverse the effects of malabsorption and chronic illness, relief of airway obstruction, and treatment of airway infection.4 Later, suppression of inflammation was also acknowledged to be key to a more favorable prognosis for those with CF. These principles remain the foundations for treatment today as we continue to develop new pharmacologic and nonpharmacologic therapies to attempt to arrest the progression of the disease and offer supportive care. However, we have as yet been able to develop a cure. Although the ultimate goal of CF therapeutics may be genetic engineering techniques that can substitute a normal gene for the mutant one, the next frontier is developing agents that correct the specific defects in the mutant forms of CFTR or underlying ion transport defects. The expansion of newborn screening for CF affords us an opportunity to treat infants earlier and improve their lives. This series discusses our current body of knowledge concerning the epidemiology, genetics, diagnosis, pathophysiology, and comprehensive treatment of CF with a look toward what the future holds for patients and their families.

Late Breaking News
At press time, the Pulmonary Therapies Committee, established by the Cystic Fibrosis (CF) Foundation, issued evidence-based recommendations regarding long-term use of medication for maintenance of lung function in patients with CF. The new guidelines are published in the November 15 issue of the American Journal of Respiratory & Critical Care Medicine.5

1.    Davis PB. Cystic fibrosis since 1938. Am J Respir Crit Care Med. 2006;173:475-482.
2.    Cystic Fibrosis Foundation Patient Registry: 2006 annual data report to the center directors; 2007.
3.    Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989;245:1073-1080.
4.    Matthews LW, Doershuk CF, Wise M, et al. A therapeutic regimen for patients with cystic fibrosis. J Pediatr. 1964;65:558-575.
5.    Flume PA, O'Sullivan BP, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007;176:957-969.

*Associate Professor of Pediatrics, Director, Cystic Fibrosis Center, Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Hospital, Baltimore, Maryland.
Address correspondence to: Peter J. Mogayzel Jr, MD, PhD, Associate Professor of Pediatrics, Director, Cystic Fibrosis Center, Eudowood Division of Pediatric Respiratory Sciences, The Johns Hopkins Hospital, 200 North Wolfe Street, Suite 3053, Baltimore, MD 21287. E-mail:

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his article and all its contents.

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