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Airway Clearance in Neonatology-Pediatric Critical Care
Abstract
Most of the important airway diseases of childhood are associated with mucus hypersecretion. Structural airway differences between children and adults are evident. Self- and assisted airway cleaning techniques are important to prevent worsening of children’s respiratory diseases.Airflow obstruction secondary to retained secretions increases the work of breathing, produces ventilation-perfusion mismatch, and can result in gas exchange abnormalities. Retained secretions can serve as a source of infection and inflammation.KeywordsAirway clearanceChildCough
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Background: Postural drainage chest physiotherapy in infants with cystic fibrosis (CF) exacerbates gastro-oesophageal reflux (GOR) and may contribute to a more rapid deterioration in lung function. Aims: To compare standard postural drainage chest physiotherapy (SPT) and a modified physiotherapy regimen (MPT) without head-down tilt, with regard to GOR, arousal state, and cardiorespiratory function. Methods: Twenty infants with CF underwent 30 hour oesophageal pH monitoring, during which four chest physiotherapy sessions were administered (day 1: MPT–SPT; day 2: SPT–MPT). Arousal state, heart rate, and oxygen saturation were documented for each of the physiotherapy positions (supine, prone, right lateral, and left lateral with (SPT) or without (MPT) 30° head-down tilt). Results: Significantly more reflux episodes occurred during SPT than during MPT, but there were no significant differences in median episode duration or fractional reflux time. During SPT, left lateral positioning was associated with fewer reflux episodes compared to other positions. During supine and prone positioning, more reflux episodes occurred during SPT than during MPT. Infants were significantly more likely to be awake or cry during SPT. There was a significant association between crying and reflux episodes for SPT. Non-nutritive sucking was associated with a significant reduction in reflux episodes during SPT. Oxygen saturation during SPT was significantly lower during crying and other waking, and non-nutritive sucking during SPT was associated with a significant increase in oxygen saturation. Conclusions: SPT is associated with GOR, distressed behaviour, and lower oxygen saturation.
Introduction:
Cystic fibrosis is an autosomal recessive disease, which is the result of a genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Pulmonary disease accounts for over 90% of the morbidity and mortality associated with the disease. Conventionally, CF treatment has focused on symptomatic therapy.
Areas covered:
In the past, the emphasis for the development of CF therapeutics has previously been on addressing complications of the manifestations rather than on the underlying disease process. However, in the past few decades there has been a paradigm shift with new attention on the underlying biological mechanisms and therapies targeted at curing the disease rather than simply controlling it. This review summarizes the current CF therapeutics pipeline. These developing therapies include CFTR gene therapy, CFTR pharmacotherapeutics, osmotically active agents and anti-inflammatory therapies, as well as novel inhaled antibiotics.
Expert opinion:
The CF therapeutics pipeline currently holds great promise both for novel therapies directly targeting the underlying biological mechanisms of CFTR dysfunction and new symptomatic therapies. While CFTR-directed therapy has the highest potential to improve patients' outcome, it is important to continue to develop better treatment options for all aspects of CF lung disease.
Background:
Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum and any therapy that reduced the number of exacerbations would be useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective.
Objectives:
To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD.
Search strategy:
We have searched the Cochrane Airways Group trials register and reference lists of articles, on three separate occasions.
Selection criteria:
Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded.
Data collection and analysis:
One reviewer extracted data. Study authors and drug companies were contacted for missing information.
Main results:
Twenty three trials were included. Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.066 per month, 95% confidence interval -0.077, -0.054, p<0.001). Using the annualised rate of exacerbations in the control patients of 2.7 per year, this is a 29% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35, p<0.001). The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.22, 95% confidence interval 1.93, 2.54, p<0.001). There was no difference in lung function or in adverse effects reported between treatments.
Reviewer's conclusions:
In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a somewhat greater reduction in total number of days of disability.
Airway mucus hypersecretion is a clinical feature of a number of childhood diseases, including asthma and bronchitis-associated conditions. However, compared with adults, there is relatively scarce information concerning mucus pathophysiology in respiratory diseases in children. The available evidence indicates many similarities between adult and childhood respiratory hypersecretory conditions, including goblet-cell hyperplasia and submucosal gland hypertrophy, and airway mucus plugging in asthma. Consequently, it is likely that treatments that are effective in adults would be effective in children. Numerous therapeutic targets are linked to the pathophysiology of airway mucus hypersecretion in experimental models and adults with respiratory disease. Whether or not these same targets are relevant in children is for the most part unclear. These targets include the inflammatory cells mediating the inflammatory response that generates the hypersecretory phenotype, and highly specific cellular elements such as epidermal growth factor receptor tyrosine kinase and calcium-activated chloride (CACL) channels. Identification of these factors is linked with the development of different classes of pharmacotherapeutic molecules directed at these targets. Compounds with a broader spectrum of anti-inflammatory activity are likely to be more effective than compounds with restricted activity. However, certain highly specific targets, such as human CACL1 channels, appear to be strongly associated with the development of an airway hypersecretory phenotype. Data from current clinical trials in adults with blockers of these specific targets are awaited with great interest. The hope is that, if effective, pediatric trials with these compounds could be initiated with a view to alleviation of the clinical impact of airway mucus hypersecretion in children. A significant challenge to the therapeutic progression of these new compounds is effective delivery to the airways in children, with the research effort into development of new compounds matched by advances in inhaler design. Pediatr Pulmonol. 2003; 36:178–188. © 2003 Wiley-Liss, Inc.
In 94 healthy children, 6–15 years of age, the intrathoracic gas volume at resting expiratory level (TGV) was measured by means of a pressure corrected flow body plethysmograph and compared to functional residual capacity (FRC), measured simultaneously to TGV by means of the Helium dilution technique. TGV is 1.9% (11.7% SD) smaller than FRC, this difference being not significant (P>0.05). A predicted equation for TGV (in ml) in correlation to standing height (in cm) is published in boys and girls.In 82 healthy children, 6–15 years of age, airway resistance (Raw) was measured plethysmographically. Raw (in cmH2O/1/s) is smaller, the larger is the child (r=-0.57; PDifficulties in the evaluation of recorded resistance curves as well as calculation and lung volume correction of the Raw-value are discussed.Bei 94 6- bis 15jhrigen gesunden Kindern wurde das intrathorakale Gasvolumen am Ende der normalen Ausatmung (TGV) mit einem druckkorrigierten, volumenvariablen Ganzkrperplethysmographen gemessen und mit der funktionellen Residualkapazitt (FRC) verglichen, die gleichzeitig mit dem TGV mit Hilfe der Heliumverdnnungsmethode bestimmt wurde. TGV ist um 1,9% (11,7% sd.) kleiner als FRC, doch ist diese Differenz statistisch nicht signifikant (P>0,05). Ein Normwertdiagramm fr TGV (in ml) bezogen auf die Krpergre (in cm) wird fr Jungen und Mdchen vorgestellt.Bei 82 6- bis 15jhrigen gesunden Kindern wurde der Atemwegswiderstand (Raw) plethysmographisch gemessen. Raw (in cmH2O/1/sec) ist kleiner, je grer das Kind ist (r=-0,57; PEs werden die Schwierigkeiten der Interpretation der Atemschleifen als auch der Berechnung und Lungenvolumenkorrektur der Raw-Werte diskutiert.
To determine whether a characteristic form of brain damage (encephaloclastic porencephaly) was associated with chest physiotherapy treatment in preterm babies.
A retrospective case-control study was undertaken among 454 infants of birth weight less than 1500 gm cared for during the 3-year period of 1992 to 1994. Thirteen babies of 24 to 27 weeks of gestation who weighed 680 to 1090 gm at birth had encephaloclastic porencephaly. Twenty-six control subjects were matched for birth weight and gestation.
The patients received two to three times as many treatments with chest physiotherapy in the second, third, and fourth weeks of life as did control infants (median 79 vs 19 treatments in the first 4 weeks, p < 0.001). Patients also had more prolonged and severe hypotension in the first week than did control subjects (median duration of hypotension 4 vs 0.5 days, p < 0.01), and were less likely to have a cephalic presentation (31% vs 81%, p < 0.01). Since December 1994 no very low birth weight baby has received chest physiotherapy treatment in the first month of life in our nursery, and no further cases have occurred.
Encephaloclastic porencephaly may be a previously unrecognized complication of chest physiotherapy in vulnerable extremely preterm infants.
The effect of postural drainage alone was compared to postural drainage with chest percussions on the arterial blood gases of 20 neonates with respiratory distress. There was no significant alteration in the arterial PO2 following postural drainage alone, with a significant increase (14.5 mm Hg) following postural drainage with chest percussions. The PO2 midway through postural drainage with percussions showed a small (5 mm Hg) but nonsignificant rise in the PO2, suggesting a gradual improvement throughout the use of this form of therapy. There was no significant change in the pH or PCO2 with either procedure. Appropriately performed chest percussions will result in an improvement in oxygenation in neonates with respiratory distress.
To investigate physiologic alterations in respiratory function associated with chest physiotherapy, arterial blood gases, respiratory patterns, lung mechanics, and functional residual capacity were measured in 13 neonates (weights 1.25 to 3.20 kg) during the control period, after vibration of the chest and suctioning, after hyperventilation, and two hours after suctioning. Compared to control values, mean PO2decreased significantly after suctioning to 43 mm Hg and increased significantly after hyperventilation to 78 mm Hg. There was a significant decrease in inspiratory resistance and a trend toward decrease in expiratory resistance after suctioning, with return to control levels after hyperventilation. Respiratory rate increased significantly after suctioning. Functional residual capacity, dynamic lung compliance, and tidal volume, as well as PCO2 and base excess, were not changed appreciably throughout the protocol. Because of potentially severe hypoxemia, this study suggests that suctioning and hyperventilation are not warranted on a routine basis in infants recovering from respiratory diseases.
We obtained maximal partial expiratory flow-volume (PEFV) curves using the rapid compression technique in three infants with intrathoracic tracheomalacia. Maximum flows were quantitated at functional residual capacity (VmaxFRC). Studies were performed at baseline, after inhalation of methacholine (MCh) and after inhalation of albuterol. At baseline, all three patients had significantly lower than normal VmaxFRC values, and two patients displayed expiratory flow limitation during tidal breathing. VmaxFRC improved significantly after MCh administration, but fell back toward or below baseline after albuterol. Additionally, the ratio of forced to tidal flows at mid-tidal volume (Vmid(forced/tidal), a reflection of expiratory flow reserve, increased after MCh administration and decreased after albuterol. Two patients also received oral bethanechol: 2.9 mg/M2, q 8 hr for 10 days, after which PEFV curves were repeated. Both Vmax FRC and Vmid(forced/tidal) were increased over baseline after bethanechol administration, but decreased after albuterol. These results suggest that in patients with abnormally collapsible tracheae, stimulation of tracheal smooth muscle can improve airway stability, thereby increasing forced expiratory flows. Additionally, relaxation of airway smooth muscle by bronchodilators can have the opposite effect and exacerbate obstruction.
The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p less than 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage.
To evaluate if chest physiotherapy is beneficial to premature infants with respiratory distress syndrome (RDS) during the first 24 hours of life, 20 infants were randomly assigned to two groups; 10 infants in Group I received routine chest physiotherapy and suction, and 10 infants in Group II received suction only. The birth weight, gestational age, postnatal age, Apgar scores, blood gases, acid-base status, and ventilatory requirements prior to study were comparable between the two groups. There were no significant differences between the groups in the amount of endotracheal secretions removed, the PO2/FIO2 ratio, blood gases, and pH during the study. The incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), Grade I and II intraventricular hemorrhage (IVH), and mortality was comparable. However, five of 10 Group I and zero of 10 Group II infants developed Grade III or IV IVH (P less than 0.05).
Development of chest wall stiffness between infancy and adulthood has important consequences for respiratory system function. To test the hypothesis that there is substantial stiffening of the chest wall in the first few years of life, we measured passive chest wall compliance (Cw) in 40 sedated humans 2 wk-3.5 yr old. Respiratory muscles were relaxed with manual ventilation applied during the Mead-Whittenberger technique. Respiratory system compliance (Crs) and lung compliance (Cl) were calculated from airway opening pressure, transpulmonary pressure, and tidal volume. Cw was calculated as 1/Cw = 1/Crs - 1/Cl during manual ventilation. Mean Cw per kilogram in infants < 1 yr old was significantly higher than that in children > 1 yr old (2.80 +/- 0.87 vs. 2.04 +/- 0.51 ml.cmH2O-1.kg-1; P = 0.002). There was an inverse linear relationship between age and mean Cw per kilogram (r = -0.495, slope -0.037; P < 0.001). In subjects with normal Cl during spontaneous breathing, Cw/spontaneous Cl was 2.86 +/- 1.06 in infants < 1 yr old and 1.33 +/- 0.36 in older children (P = 0.005). We conclude that in infancy the chest wall is nearly three times as compliant as the lung and that by the 2nd year of life chest wall stiffness increases to the point that the chest wall and lung are nearly equally compliant, as in adulthood. Stiffening of the chest wall may play a major role in developmental changes in respiratory system function such as the ability to passively maintain resting lung volume and improved ventilatory efficiency afforded by reduced rib cage distortion.
To determine the clinical effects of a change from postural drainage (PD) to positive expiratory pressure chest physiotherapy (PEP) in children with cystic fibrosis (CF) and symptoms of gastro-oesophageal reflux (GOR). To measure the effects of PD on GOR in children with CF.
Study 1: Six adolescents with CF and symptoms of GOR during PD were changed to upright PEP physiotherapy. The effects on lung function, reflux symptom scores and annual hospital days were measured. Study 2: Twenty-four children with CF (mean age 11 years) and symptoms suggestive of GOR underwent 24-h pH monitoring, including periods of chest physiotherapy.
Study 1: All six patients reported a reduction in reflux symptoms during PEP therapy (P < 0.001). Lung function parameters improved during the first 6 months of PEP (P < 0.001). This improvement was sustained for a further 18 months. Annual hospital days decreased significantly (P < 0.0005). Study 2: Nine of 24 patients (37.5%) had pathological GOR. Reflux episodes were significantly increased during PD (P < 0.0001), as was fractional reflux time (P < 0.01).
Upright PEP physiotherapy may be more appropriate than PD in selected patients with CF and symptomatic GOR. The role of GOR as a cofactor in the progression of pulmonary disease in CF needs further evaluation.
The model of the lung as an elastic continuum undergoing small distortions from a uniformly inflated state has been used to describe many lung deformation problems. Lung stress-strain material properties needed for this model are described by two elastic moduli: the bulk modulus, which describes a uniform inflation, and the shear modulus, which describes an isovolume deformation. In this study we measured the bulk modulus and shear modulus of human lungs obtained at autopsy at several fixed transpulmonary pressures (Ptp). The bulk modulus was obtained from small pressure-volume perturbations on different points of the deflation pressure-volume curve. The shear modulus was obtained from indentation tests on the lung surface. The results indicated that, at a constant Ptp, both bulk and shear moduli increased with age, and the increase was greater at higher Ptp values. The micromechanical basis for these changes remains to be elucidated.
Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon gamma. There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosinophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD8 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance and importance of CD4/CD8 T lymphocyte ratio to the development of COPD is discussed.
Many acute and chronic respiratory diseases are associated with increased respiratory secretions in the airways. Narrative reviews and a few systematic reviews of secretion clearance techniques have been published. These reviews raise concerns regarding the lack of evidence to support the various secretion clearance techniques. I conducted a comprehensive MEDLINE search of the following subjects: chest physical therapy, chest physiotherapy, postural drainage, forced expiratory technique, autogenic drainage, high-frequency chest wall compression, flutter device and secretions, positive expiratory pressure and secretions, intrapulmonary percussion, mechanical in-exsufflation and secretions. This was followed by a comprehensive search of cross-references to identify additional studies. The results of this review are reported herein. There are a number of methodological limitations of the literature reporting studies of the use of secretion clearance techniques. Most of the studies were small, most used crossover designs, and few used sham therapy. Many studies were limited to short-term outcomes such as sputum clearance with a single treatment session. Despite the clinical observation that retained secretions are detrimental to respiratory function and despite anecdotal associations between secretion clearance and improvements in respiratory function, there is a dearth of high-level evidence to support any secretion clearance technique.
Chest physiotherapy has been used to clear secretions and help lung ventilation in newborns who have needed mechanical ventilation for respiratory problems. However concerns about the safety of some forms of chest physiotherapy have been expressed.
To assess the effects of active chest physiotherapy on babies being extubated from mechanical ventilation for neonatal respiratory failure.
The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials; Cochrane Controlled Trials Register (Cochrane Library Issue 4 2001); MEDLINE (1966-2001); and CINAHL (1982-2001), previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language.
All trials utilising random or quasi-random patient allocation, in which active chest physiotherapy was compared with non-active techniques (eg positioning and suction alone) or no intervention in the periextubation period.
Assessment of methodological quality and extraction of data for each included trial was undertaken independently by the authors. Data were extracted for the primary outcomes of postextubation lobar collapse, use of reintubation, duration of oxygen therapy, intracranial haemorrhage, cerebral cystic lesions, long term neurosensory impairment and death. Subgroup analysis was performed on different treatment frequencies and gestational age less than 32 weeks. Meta-analysis was conducted using a fixed effects model. Results are presented as relative risk (RR), risk difference (RD) and number needed to treat (NNT) for categorical data and mean difference (MD) for data measured on a continuous scale. All outcomes are reported with the use of 95% confidence intervals.
In this review of four trials, two of which were carried out 15 & 23 years ago, no clear benefit of periextubation active chest physiotherapy can be seen. Active chest physiotherapy did not significantly reduce the rate of postextubation lobar collapse [RR 0.80 (95% CI 0.49,1.29)], though a reduction in the use of reintubation was shown in the overall analysis: RR 0.32 (95% CI 0.13,0.82); RD -7% (95% CI-13, -2); NNT 14 (95% CI 8, 50). There is insufficient information to adequately assess important short and longer term outcomes, including adverse effects.
The results of this review do not allow development of clear guidelines for clinical practice. Caution is required when interpreting the possible positive effects of chest physiotherapy of a reduction in the use of reintubation and the trend for decreased post-extubation atelectasis as the numbers of babies studied are small, the results are not consistent across trials, data on safety are insufficient, and applicability to current practice may be limited. Further randomised controlled trials addressing the role of prophylactic active chest physiotherapy for neonates in the postextubation period may be unwarranted.
The reported causes of rib fractures in infants are: child abuse, accidental injury, cardiopulmonary resuscitation, bone fragility, birth trauma and severe cough.
To report chest physiotherapy (CPT) as a new cause of rib fractures in five infants.
We retrospectively identified all infants with rib fractures after CPT for bronchiolitis or pneumonia over a 4-year period in two paediatric and one paediatric radiology units in three university hospitals in Paris.
Five boys were identified. Their median age was 3 months. None had any other potential cause of rib fractures. The indication for CPT was bronchiolitis in four cases and pneumonia in one. The median number of rib fractures was four (range 1-5). Fractures were located between the 3rd and 8th ribs; they were lateral in four patients and posterior in one; they were unilateral in four patients and bilateral in one. Evolution was favourable in all cases. The prevalence of rib fractures after CPT during the study period was estimated at 1 in 1,000 infants hospitalised for bronchiolitis or pneumonia.
CPT should be considered a potential, but very rare cause of rib fractures in infants. It can be of clinical relevance when rib fractures are the only feature suggestive of child abuse.
Background:
Cystic fibrosis is an inherited life-limiting disorder, characterised by pulmonary infections and thick airway secretions. Chest physiotherapy has been integral to clinical management in facilitating removal of airway secretions. Conventional chest physiotherapy techniques (CCPT) have depended upon assistance during treatments, while more contemporary airway clearance techniques are self-administered, facilitating independence and flexibility.
Objectives:
To compare CCPT with other airway clearance techniques in terms of their effects on respiratory function, individual preference, adherence, quality of life and other outcomes.
Search strategy:
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched CINAHL from 1982 to 2002 and AMED from 1985 to 2002. Date of most recent search: January 2004.
Selection criteria:
Randomised or quasi-randomised clinical trials including those with a cross-over design where CCPT was compared with other airway clearance techniques. Studies of less than seven days duration were excluded.
Data collection and analysis:
Two reviewers allocated quality scores to relevant studies and independently extracted data. If we were unable to extract data, we invited authors to submit their data. We excluded studies from meta-analysis when data were lost or study design precluded comparison. For some continuous outcomes, we used the generic inverse variance method for meta-analysis of data from cross-over trials and data from parallel-designed trials were incorporated for comparison. We also examined efficacy of specific techniques and effects of treatment duration.
Main results:
Seventy-eight publications were identified by the searches. Twenty-nine of these were included, representing 15 data sets with 475 participants. There was no difference between CCPT and other airway clearance techniques in terms of respiratory function measured by standard lung function tests. Studies undertaken during acute exacerbations demonstrated relatively large gains in respiratory function irrespective of airway clearance technique. Longer-term studies demonstrated smaller improvements or deterioration over time. Ten studies reported individual preferences for technique, with participants tending to favour self-administered techniques. Heterogeneity in the measurement of preference precluded these data from meta-analysis.
Authors' conclusions:
This review demonstrated no advantage of CCPT over other airway clearance techniques in terms of respiratory function. There was a trend for participants to prefer self-administered airway clearance techniques. Limitations of this review included a paucity of well-designed, adequately-powered, long-term trials.
This review examines specific mucoactive agents from three classes: expectorants, which add water to the airway; ion-transport modifiers, which promote ion and water transport across the epithelium of the airway; and mucokinetics, which improve cough-mediated clearance by increasing airflow or reducing sputum adhesivity. The agents are isotonic and hypertonic saline, mannitol, denufosol and beta-agonists. Our understanding of these agents has recently improved through pre-clinical research, clinical trials and, in particular, extensive research into the nature of the liquid lining the surface of the airway, both in health and in cystic fibrosis (CF). For each agent, recent research is reviewed, highlighting the evidence for possible mechanisms of action and for clinical efficacy in CF, as well as the implications for the optimal clinical application of the agent.
Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future.
Mucus secretion is the first-line defense against the barrage of irritants that inhalation of approximately 500 L of air an hour brings into the lungs. The inhaled soot, dust, microbes, and gases can all damage the airway epithelium. Consequently, mucus secretion is extremely rapid, occurring in tens of milliseconds. In addition, mucus is held in cytoplasmic granules in a highly condensed state in which high concentrations of Ca(2+) nullify the repulsive forces of the highly polyanionic mucin molecules. Upon initiation of secretion and dilution of the Ca(2+), the repulsion forces of the mucin molecules cause many-hundred-fold swelling of the secreted mucus, to cover and protect the epithelium. Secretion is a highly regulated process, with coordination by several molecules, including soluble N-ethyl-maleimide-sensitive factor attachment protein receptor (SNARE) proteins, myristoylated alanine-rich C kinase substrate (MARCKS), and Munc proteins, to dock the mucin granules to the secretory cell membrane prior to exocytosis. Because mucus secretion appears to be such a fundamental airway homeostatic process, virtually all regulatory and inflammatory mediators and interventions that have been investigated increase secretion acutely. When given longer-term, many of these same mediators also increase mucin gene expression and mucin synthesis, and induce goblet cell hyperplasia. These responses induce (in contrast to the protective effects of acute secretion) long-term, chronic hypersecretion of airway mucus, which contributes to respiratory disease. In this case the homeostatic, protective function of airway mucus secretion is lost, and, instead, mucus hypersecretion contributes to pathophysiology of a number of severe respiratory conditions, including asthma, chronic obstructive pulmonary disease, and cystic fibrosis.
Clinicians and their patients are troubled by respiratory secretions, and standard practice calls for efforts to clear secretions from the lungs. On one hand, mucus production and cough are important for airway defense and protection of the lower respiratory tract against inhaled irritations. On the other hand, excessive mucus obstructs airways and excessive cough has been associated with a number of complications. The objective of this conference was to review the scientific basis and clinical evidence for the use of airway clearance therapy to guide the most appropriate approach to airway clearance. An international group of clinicians and scientists addressed the physiology of mucus production and cough, pharmacologic approaches to airway clearance, and the variety of techniques available for airway clearance. Specific issues related to airway clearance in critically ill patients, children, and the elderly were discussed. Outcome measures related to evaluating mucus clearance therapy were also presented. One of the themes repeated consistently throughout this conference was the dearth of high-level evidence related to airway clearance techniques. Appropriately powered and methodologically sound research is desperately needed in this area.
The rationale for airway clearance therapy and basic principles of its application are identical for children and adults, but there are important differences in physiology (regarding airway mucus characteristics and airway mechanics) and pathological processes in children, as well as other considerations unique to the pediatric population. The major obstacle in reviewing the evidence for efficacy of airway clearance therapy in pediatrics is the lack of data from well-performed, adequately powered clinical trials. This problem is partially alleviated by the use of published meta-analyses. A review of pediatric studies suggests that airway clearance therapy is of clear and proven benefit in the routine care of cystic fibrosis, and that no specific airway-clearance technique is clearly superior, but for any individual patient the technique that is most likely to maximize patient adherence to treatment is preferred. Airway clearance therapy appears likely to be of benefit in the routine care of children with neuromuscular disease and cerebral palsy, and is probably of benefit in treating atelectasis in children on mechanical ventilation. Airway clearance therapy may be of benefit in preventing post-extubation atelectasis in neonates. Airway clearance therapy appears to be of minimal to no benefit in the treatment of children with acute asthma, bronchiolitis, hyaline membrane disease, and those on mechanical ventilation for respiratory failure in the pediatric intensive care unit, and it is not effective in preventing atelectasis in children immediately following surgery. All in all, however, given that these conclusions are based on very little data, future well-performed clinical trials might change the weight of evidence to contradict these current conclusions.
Physiotherapy for airway clearance in paediatrics
- B Oberwaldner