This comprehensive State of the Art review summarizes the current published knowledge base regarding the pathophysiology and microbiology of pulmonary disease in cystic fibrosis (CF). The molecular basis of CF lung disease including the impact of defective cystic fibrosis transmembrane regulator (CFTR) protein function on airway physiology, mucociliary clearance, and establishment of Pseudomonas aeruginosa infection is described. An extensive review of the microbiology of CF lung disease with particular reference to infection with P. aeruginosa is provided. Other pathogens commonly associated with CF lung disease including Staphylococcal aureus, Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans and atypical mycobacteria are also described. Clinical presentation and assessment of CF lung disease including diagnostic microbiology and other measures of pulmonary health are reviewed. Current recommendations for management of CF lung disease are provided. An extensive review of antipseudomonal therapies in the settings of treatment for early P. aeruginosa infection, maintenance for patients with chronic P. aeruginosa infection, and treatment of exacerbation in pulmonary symptoms, as well as antibiotic therapies for other CF respiratory pathogens, are included. In addition, the article discusses infection control policies, therapies to optimize airway clearance and reduce inflammation, and potential future therapies.

Pathophysiology and management of pulmonary infections in cystic fibrosis.

The forced oscillation technique in clinical practice: methodology, recommendations and future developments. E. Oostveen, D. MacLeod, H. Lorino, R. Farre´ , Z. Hantos, K. Desager, F. Marchal, on behalf of the ERS Task Force on Respiratory Impedance Measurements. #ERS Journals Ltd 2003. ABSTRACT: The forced oscillation technique (FOT) is a noninvasivemethod with which to measure respiratory mechanics. FOT employs small-amplitude pressure oscillations superimposed on the normal breathing and therefore has the advantage over conventional lung function techniques that it does not require the performance of respiratory manoeuvres. The present European Respiratory Society Task Force Report describes the basic prin- ciple of the technique and gives guidelines for the application and interpretation of FOT as a routine lung function test in the clinical setting, for both adult and paediatric populations. FOT data, especially those measured at the lower frequencies, are sensitive to airway obstruction, but do not discriminate between obstructive and restrictive lung disorders. There is no consensus regarding the sensitivity of FOT for bronchodilation testing in adults. Values of respiratory resistance have proved sensitive to bronchodilation in children, although the reported cutoff levels remain to be cone rmed in future studies. Forced oscillation technique is a reliable method in the assessment of bronchial hyper- responsiveness in adults and children. Moreover, in contrast with spirometry where a deep inspiration is needed,forced oscillation techniquedoes not modifytheairway smooth muscle tone. Forced oscillation technique has been shown to be as sensitive as spirometry in detecting impairments of lung function due to smoking or exposure to occupational hazards. Together with the minimalrequirement for the subject 9s cooperation, this makes forced oscillation technique an ideal lung function test for epidemiological and e eld studies. Novel applications of forced oscillation technique in the clinical setting include the monitoring of respiratory mechanics during mechanical ventilation and sleep.

https://erj.ersjournals.com/content/erj/22/6/1026.full.pdf

The forced oscillation technique in clinical practice: methodology, recommendations and future developments

Nicole Beydon, Stephanie D. Davis, Enrico Lombardi, Julian L. Allen, Hubertus G. M. Arets, Paul Aurora, Hans Bisgaard, G. Michael Davis, Francine M. Ducharme, Howard Eigen, Monika Gappa, Claude Gaultier, Per M. Gustafsson, Graham L. Hall, Zoltán Hantos, Michael J. R. Healy, Marcus H. Jones, Bent Klug, Karin C. Lødrup Carlsen, Sheila A. McKenzie, François Marchal, Oscar H. Mayer, Peter J. F. M. Merkus, Mohy G. Morris, Ellie Oostveen, J. Jane Pillow, Paul C. Seddon, Michael Silverman, Peter D. Sly, Janet Stocks, Robert S. Tepper, Daphna Vilozni, and Nicola M. Wilson, on behalf of the American Thoracic Society/ European Respiratory Society Working Group on Infant and Young Children Pulmonary Function Testing

An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children.

During the last decade, there have been enormous advances in our knowledge of glycoproteins and the stage has been set for the biotechnological production of many of them for therapeutic use. These advances are reviewed, with special emphasis on the structure and function of the glycoproteins (excluding the proteoglycans). Current methods for structural analysis of glycoproteins are surveyed, as are novel carbohydrate-peptide linking groups, and mono- and oligo-saccharide constituents found in these macromolecules. The possible roles of the carbohydrate units in modulating the physicochemical and biological properties of the parent proteins are discussed, and evidence is presented on their roles as recognition determinants between molecules and cells, or cell and cells. Finally, examples are given of changes that occur in the carbohydrates of soluble and cell-surface glycoproteins during differentiation, growth and malignancy, which further highlight the important role of these substances in health and disease.

Protein glycosylation. Structural and functional aspects.

Glycosylation is a common post-translational modification to cell surface and extracellular matrix (ECM) proteins as well as to lipids. As a result, cells carry a dense coat of carbohydrates on their surfaces that mediates a wide variety of cell-cell and cell-matrix interactions that are crucial to development and function. Because of the historical difficulties with the analysis of complex carbohydrate structures, a detailed understanding of their roles in biology has been slow to develop. Just as mass spectrometry has proven to be the core technology behind proteomics, it stands to play a similar role in the study of functional implications of carbohydrate expression, known as glycomics. This review summarizes the state of knowledge for the mass spectrometric analysis of oligosaccharides with regard to neutral, sialylated, and sulfated compound classes. Mass spectrometric techniques for the ionization and fragmentation of oligosaccharides are discussed so as to give the reader the background to make informed decisions to solve structure-activity relations in glycomics.

Mass spectrometry of oligosaccharides.

Disulfated oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis.

To determine the effects of acute viral respiratory infections (ARI) in cystic fibrosis (CF) we studied all episodes of ARI in ten patients over a 2 year period. A daily diary card was kept on which they recorded all illnesses, including specific upper and lower respiratory symptoms, antibiotic use, and daily peak flow measurements. Recording of concurrent similar illnesses in other household members aided in confirming the onset of ARI, as did a home viral culturing technique and serial serum antibody levels against specific viral types. A total of 80% of the 35 recorded onsets of ARI (1.75/yr/subject) were confirmed by one or more of these methods. Five subjects with moderate to severe pulmonary function scores at the outset of the study had significantly greater decreases in PEFR during ARI episodes (42.4%) than those with milder disease (15.4%), and it took them significantly longer to recover to their baseline measurements (22 days vs. 15 days respectively). The majority of hospital admissions for pulmonary exacerbations were preceded by viral infections (7/8). Pediatr Pulmonol 1989; 7:217–222.

Effects of acute viral respiratory tract infections in patients with cystic fibrosis.

An investigator-designed survey was used to determine if attendance at specific continuing education programs increased the perceived competence of school nurses who enrolled and completed the programs. Respondents were queried about the general content of six courses offered by the Missouri Department of Health and Senior Services in conjunction with the University of Missouri-Columbia Sinclair School of Nursing. Specific content areas were mental health concerns, suicide prevention, diabetes management, asthma management, seizure disorders, and developing clinical skills as they pertained to school-age children. Comparing a sample of school nurses who had attended the programs with a group whom had not, a statistically significant difference was found in the participant group who reported higher self-perceived competence than the nonparticipant group in all content areas. Results of the study suggest that school nurses who attend specific continuing education programs feel more competent in practice than nurses who do not attend.

Continuing Education: Improving Perceived Competence in School Nurses:

Structural analysis of monosulfated side-chain oligosaccharides isolated from human tracheobronchial mucous glycoproteins.

The effectiveness of maintenance albuterol aerosol therapy in cystic fibrosis (CF) was assessed by comparing spirometric measurements at the beginning and end of 1 year. Peak expiratory flow rates (PEFR) were measured twice daily to determine bronchodilator responsiveness and spontaneous diurnal variation (SDV), and results were compared with groups of normal and asthmatic children. CF patients not receiving regular albuterol therapy served as a control group. In the treatment group, forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were significantly increased (12.2% and 18.4%, respectively) over the course of the treatment year, as contrasted with a significant decrease during the preceding year. During the study year the CF control group had a significant decrease in FEV1 and FEF25-75%, and the difference between treatment and control groups was significant for FVC, FEV1, and FEF25-75%. PEFR increased from the first to the last week of the year-long observation period (from 71.8% to 78.7% of predicted values, P 15% was present in 25.8% of CF patient days, but there was considerable interpatient variability. Frequent bronchodilator responders were accurately predicted by their baseline bronchodilator responsiveness, but not by age or personal or family history of asthma or atopy. No difference in long-term pulmonary function improvements were noted between frequent and infrequent responders. The results suggest that maintenance albuterol aerosol treatments reversed the progressive downward course in lung function in the CF treatment group. A double-blind placebo-controlled study is required to confirm these preliminary findings.

Debra Gayer

Papers

Disulfated oligosaccharides derived from tracheobronchial mucous glycoproteins of a patient suffering from cystic fibrosis.

Effects of acute viral respiratory tract infections in patients with cystic fibrosis.

Continuing Education: Improving Perceived Competence in School Nurses:

Structural analysis of monosulfated side-chain oligosaccharides isolated from human tracheobronchial mucous glycoproteins.

Short-term and long-term effects of albuterol aerosol therapy in cystic fibrosis: a preliminary report.