Disorders that impair mucociliary transport can occur in as many as 1 in 3,000 births.
Airway clearance is the ability to maintain a clean environment in the lower airways. The lung can be thought of as a dead-end street: Particulate matter that gets into the lung must leave using the same route through which it entered. Keeping the airways cleared requires a combination of two distinct, but equally important, mechanisms: mucociliary transport and cough clearance. Humans need both in order to maintain the hygiene of the lower airways. The mucociliary escalator moves a thin layer of mucus toward the airway opening; once a bolus of material reaches the central airways, the presence of the material is sensed. It is then expelled via cough clearance. In pediatric populations, many congenital diseases, infections, and environmental factors can impair the ability to clear the lower airways.
Most airway epithelial cells have cilia on their apical surfaces. Each cell contains approximately 200 cilia, which beat 200 times per second in a coordinated fashion. The ultrastructure of the cilium is an arrangement of nine doublets arranged around a central pair. The doublets are connected by dynein, which is an adenosine triphosphatase (ATPase) that allows the tubules to slide over one another actively. The mechanism of the ciliary beating requires specialized organelles that whip in a two-cycle stroke: a forward-pushing effective phase and a reverse recovery phase. The cilia sit in the airways surface liquid in an aqueous sol layer; the tip of each cilium at full extension grabs the gel layer of mucus that sits atop the sol layer and pushes it forward.
There are two congenital diseases that impair mucociliary transport: primary ciliary dysmotility (PCD), also referred to as immotile-cilia syndrome and Kartagener syndrome, and cystic fibrosis (CF). In the most common form of PCD, the cilia are missing the outer dynein arm, cannot use ATP, and are paralyzed as a result. Chronic stasis of secretions leads to chronic infections of the ciliated surfaces, including the sinuses, the airways, and the middle ears. Half of PCD patients have situs inversus.1 Bronchiectasis eventually occurs as a result of the chronic infection.
CF impairs mucociliary transport by reducing the amount of airway-surface liquid. As a result, the cilia are matted down and unable to beat freely to clear the airways. Chronic stasis also leads to chronic infection, chronic inflammation, and a damaging positive-feedback loop. Unless airway clearance is directly addressed, both diseases lead to an inexorable decline in lung function, with increasingly severe obstructive lung disease and death from respiratory failure. CF occurs in approximately 1 in 3,000 births in white populations.2 The actual incidence of PCD is unknown, but is likely to be on the scale of 1 in 16,000 births.1 More common than either of these congenital diseases is acquired impairment of the mucociliary escalator. Children exposed to secondhand smoke have, in essence, acquired ciliary dyskinesia and have an increased incidence of otitis media, bronchitis, pneumonia, and asthma. Certain infections of the lower airways, including nearly all respiratory viruses, can damage the cilia and lead to widespread temporary loss of cilia. Occasionally, the cilia do not recover properly, leading to permanent damage to the airways and to postinfectious bronchiectasis.
Coughing is a highly controlled reflex with defined phases. The initial (inspiratory) phase of coughing requires a maximal inspiration in order to get air behind the mucus or debris that needs to be cleared. The next (compressive) phase actually consists of two separate actions: glottic closure and contraction of the abdominal muscles. These allow the intrathoracic pressure to rise, compressing the central airways. The significance of the compressive phase is dual. Narrowing the airways makes the velocity of the airflow higher, and increasing the intrathoracic pressure creates a strong driving force for the expulsion of secretions. Measured pressures in children have exceeded 100 cm H2O.3 In the last (expulsive) phase of coughing, air is released at a high velocity, carrying with it mucus and debris.
Any aspect of cough clearance can be impaired. Inability to take a deep breath is commonly seen in patients with neuromuscular weakness, as seen in Duchenne muscular dystrophy or spinal-cord injury. The compressive phase is impaired if there is poor airway control (as seen in severe cerebral palsy) or weakness in the abdominal musculature.
It should be possible to predict which patients will have impaired cough clearance using pulmonary function testing. Although there is no single test that should be used to make decisions regarding the institution of assisted coughing, Bach et al at the University of Medicine and Dentistry of New Jersey, Newark, have used peak flows (or peak cough flows, as measured using a peak flow meter during a cough) of 270 L per minute as the lower limit of normal for adults.4 In children, we have used limits of forced vital capacity of less than 50% of the predicted value and peak expiratory pressure of less than 60 cm H2O. Even more useful is the simple finding, in the patients medical history, of difficulty with cough clearance. Parents will report that their children have excessive difficulty in clearing the airways and that colds seem to linger. A past history of pneumonia in a patient with known neuromuscular weakness should raise ones index of suspicion for impaired cough clearance.
It is especially important for patients with impaired cough clearance to eliminate cigarette smoke from the environment, since these patients rely more on mucociliary clearance than cough clearance for maintenance of lower airway hygiene. Smoking in the home of a patient with Duchenne muscular dystrophy is more than dangerous; it borders on abusive. Similarly, it is necessary to avoid passive smoke exposure in any patient who has underlying deficits of airway clearance.
Managing Airway Clearance
The management of diseases of airway clearance depends on whether the primary disorder is of the mucociliary escalator or of cough clearance. Traditional percussion with postural drainage (chest physiotherapy) is quite useful, despite the labor-intensive nature of this therapy. Its efficacy was demonstrated in early studies.5 All respiratory therapists are taught this technique, and, as one walks down the corridors in any pediatric hospitals adolescent wing, one can hear the rhythmic clapping as CF patients undergo this procedure. Recently, reports6 have demonstrated that head-down positioning for chest physiotherapy is to be avoided, as it increases gastroesophageal reflux.
Increasingly, patients with CF are using automated mechanical devices for airway clearance. These devices vibrate the chest using high-frequency chest-wall oscillation (HFCWO). The airway-clearance techniques that are easiest to use probably tend to have the best compliance, and this may account for the success of HFCWO. Although unproven in other settings, HFCWO has been used in other disease states in which there is chronic stasis of the lower-airway secretions, such as PCD and cerebral palsy with chronic aspiration. I do not recommend its use in patients with neuromuscular weakness who do not have chronic lower-airway secretions. These devices are fairly expensive, and prior authorization and letters of medical necessity may be required before some insurance carriers will cover their use.
I like to have my patients with primary diseases of mucociliary clearance (such as CF and PCD) obtain a handheld device. These devices oscillate a column of air within the lungs and help loosen adherent secretions. They are less expensive and more portable than HFCWO machines and are useful if a patient needs to undergo airway-clearance therapy at school, in a car, or anywhere away from home. They are of proven efficacy,7 so long as they are used regularly. Achieving compliance with any airway-clearance device is the secret of success in managing these patients.
Recombinant human DNase is used in patients with CF to thin tenacious secretions by clipping free DNA and indirectly improving airway clearance. Hypertonic (7%) saline has been demonstrated to improve lung function in CF in a number of studies recently reviewed.8 The mechanisms are increased airway-surface liquid and improved ciliary beating. At this time, the review authors are not advocating its routine use in CF, but this therapy is gaining acceptance in the CF-care community. Hypertonic saline is the only therapy that directly addresses the imbalance in airway-surface liquid and the impaired mucociliary escalator in CF in use today, and it is going to be used increasingly in this patient population.
Although mechanically assisted coughing has been used as long as there has been a mechanism to inflate the lungs, the benefit of assisted coughing did not become apparent until the widespread use of mechanically assisted coughing (mechanical insufflation-exsufflation) began. Any child with neuromuscular weakness affecting the muscles of breathing and coughing is likely to benefit from mechanical insufflation-exsufflation. This technique allows a maximal breath to be insufflated into the lungs, then rapidly exsufflated. The newer devices are easy to use and their acceptance appears to be growing. They are recommended in the American Thoracic Societys consensus statement9 on the respiratory management of Duchenne muscular dystrophy. In my own practice, I have instructed families to use the mechanical insufflator-exsufflator twice daily when their children are well and more frequently during illnesses. The applicable theory is that frequent, maximal insufflation of the chest will prevent the development of rigidity of the chest well secondary to contractures of the intercostal muscles. This therapy is underutilized in the pediatric world and should benefit any patient who is unable to cough due to any impairment in cough efficacy. It has not been used in postoperative patients with normal strength whose coughs are impaired by abdominal pain; this is an area that remains to be studied.
Airway clearance is the primary focus in caring for children with CF, PCD, and neuromuscular weakness. One must determine if the deficit is one of mucociliary transport. If so, mechanical therapies coupled with pharmacological therapies to improve airway clearance are indicated. If cough clearance is impaired, assisted coughing is indicated. Taking an aggressive approach to airway clearance in the pediatric population with chronic diseases of the lower airways is critical to maintaining the health of these children.
Jonathan D. Finder, MD, is associate professor of pediatrics, University of Pittsburgh School of Medicine.
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