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Cls175 bronchiectasis overviewAirway Clearance Indications in
Bronchiectasis: An Overview
Jane M. Braverman, Ph.D.
Employed by Hill-Rom
Dr. Jane Braverman has experience in laboratory, academic, and technological medicine. She has worked as a medical technologist in basic research at the University of Minnesota and in clinical laboratory medicine at Twin Cities hospitals. After earning her Ph.D., she served as assistant professor in the Department of the History of Medicine at the University of Minnesota. Dr. Braverman, as research analyst/writer for Hill-Rom, has contributed to a variety of research endeavors and developed white papers, case studies, and other supporting materials.
Airway Clearance Indications in Bronchiectasis:
Jane M Braverman, Ph.D.
Bronchiectasis is a pathological process characterized by irreversible dilation and destruction of bronchialwalls. The condition may be confined to a single pulmonary lobe or segment, or may involve multiplepulmonary segments or lobes, frequently associated with chronic bronchitis.1 Because persistent orrecurrent airflow limitation is a distinguishing feature, it is classified generically as one of the chronicobstructive pulmonary diseases (COPDs). Bronchiectasis is a consequence of a broad variety of primarydisease processes and should not be regarded as a single diagnostic entity. Instead, the condition is bestunderstood as the final common pathway of a series of structural and functional alterations created byspecific pathological mechanisms.2 The clinical features of the COPDs frequently overlap. Bronchiectasis is distinguished by the intensity ofits inflammation.3,4 As a result, mucociliary clearance is compromised, bronchopulmonary infectionsoccur, and copious secretions pool throughout the bronchial tree. These events characterize a vicious cycleof recurrent inflammation, infection, and permanent pulmonary damage with bronchial dilation, i.e.
bronchiectasis.5,6 History and Epidemiology
Evidence reported in the recent literature indicates thatcurrently, bronchiectasis is frequently underrecognized and Before the advent of antibiotics and the widespread underdiagnosed. Moreover, until recently, understanding practice of immunizing against childhood diseases, of the etiology and pathogenesis of bronchiectasis has been bronchiectasis was a common condition, and the prognosis was generally poor.7,8 A report published in 1940 based on epidemiological and scientific aspects have prompted follow-up of 400 individuals with bronchiectasis states that renewed interest in the study of bronchiectasis: bronchiectasis was the primary or secondary cause in 92%of the mortality. Seventy percent of fatalities occurred Epidemiological factors
• Bronchiectasis is now recognized as a major manifestation of disease progression in cystic fibrosis Beginning in the mid 1950s, however, immunization (CF), ciliary dyskinetic syndromes, and some immune campaigns and effective antimicrobial agents caused a deficiency syndromes. The increased survival of such sharp reduction in the incidence of childhood infections.
patients in response to therapeutic advances is The prognosis for bronchiectasis improved, and its associated with a sharp increase in clinically prevalence declined. A 1969 study reported 50% of significant bronchiectasis.18,19 In Western Europe and bronchiectasis patients died of their disease, but at an the U.S., cystic fibrosis is the leading cause of average age of 55.10 By the 1970s, fewer than 10% of patients included in follow-up studies died of that cause.11 computed tomographic assessments of pulmonaryinvolvement of 117 CF patients ranging in age from Recently however, bronchiectasis has reemerged as a infancy to adult, 80% demonstrated bronchiectasis.21 serious health risk; especially in less developed countries, In studies limited to adult patients, 90-100% and among population subgroups where preventive and therapeutic interventions are poorly distributed.12,13 A 1981 review of 116 British patients followed for 14 yearsreported that 19% died of bronchiectasis at an average age • As a concomitant of the HIV epidemic, there have of 54.14 In Finland, a nation with exemplary healthcare been dramatic rises in the incidence of opportunistic services, a 1997 study of 842 individuals aged 35-74 with infections, including Pneumocystis carinii and bronchiectasis reported significant morbidity and a pulmonary tuberculosis. In affected individuals, bronchiectasis may develop rapidly.24 The majority ofimmune-compromised symptomatic lung disease show radiologic evidence of • postinfective bronchial damage (bacterial, viral, fungal, • Bronchiectasis is recognized as an important • mechanical bronchial obstruction (foreign body, tumor, complication of heart, lung, and bone marrow transplantation related to recurrent infection and graft • congenital structural abnormalities (bronchial wall • immune deficiency (hypogammaglobulinemia, HIV, Scientific factors
• High resolution computed tomography (HRCT) has • immunological hyperresponse (allergic revolutionized the imaging of bronchi, allowing early bronchopulmonary aspergillosis, post-organ transplant detection and providing new information.28 It is now possible to detect bronchiectasis early. Recognition of • mucociliary clearance defects (cystic fibrosis, primary associated clinical manifestations add to understanding and secondary ciliary dyskinesia, Young's syndrome) of associations between clinical features and structural • granulomata and fibrosis (tuberculosis, sarcoidosis, etc.) abnormalities in the airways is progressing.29 Pathology/Pathogenesis
• Recent studies of mycobacterial diseases, including tuberculosis, suggest that these organisms have both The pathology of bronchiectasis covers a broad spectrum. The primary and secondary roles in bronchiectasis.30 primary feature of the condition, marked dilation of theairways in affected regions of the lung, is visible on gross • Genetics advances have stimulated research to inspection. Three specific patterns of airway dilation are recognized; cylindrical, varicose, and saccular.40 For practical purposes, however, morphologic classification is not asrelevant as the extent of mucociliary dysfunction.41 Etiology
In the pathogenic sequence recognized in bronchiectasis, Bronchiectasis is a destructive, self-perpetuating process bronchial dilation, inflammation, and weakening cause initiated by a broad spectrum of clinical diseases and airway distortion and scarring, altering both the structure and conditions. In general, infection and obstruction are the function of the mucociliary apparatus. Secretion clearance is underlying causes leading to the development of dilated impaired. Bronchial inflammation, characterized by i.e. bronchiectatic airways.34 Today, causative organisms neutrophil infiltration, results in increased protease activity, are most commonly opportunistic and frequently which in turn leads to more mucus hypersecretion and further antibiotic-resistant, rather than the generic childhood airway destruction. In addition, the toxic byproducts of bacterial or viral infections of the past.35 Airway inflammation precipitate rheological changes in airway obstruction in bronchiectasis occurs as a consequence of mucus, and it becomes thick and tenacious.42 Typically, mucus plugging associated either with the infectious affected passages are filled with large quantities of frequently process or with a defect in mucociliary clearance.36 The purulent mucus. Microscopic examination of bronchial tissues list of clinical conditions predisposing to infection or demonstrate severe damage to squamous epithelia, cilia, and obstruction is impressive, and includes hilar adenopathy, aspirated foreign bodies, congenital tracheobronchial,vascular, or lymphatic anomalies and tumors. Three major mechanisms contribute to the destruction ofbronchial tissue: infection, airway obstruction, and Previously, certain genetic abnormalities were presumed significant factors in bronchiectasis. However, recentresearch suggests that although a complex array of Infection and inflammation
factors, including genetic disease, may increase Inflammation, usually initiated by infection, is recognized susceptibility to bronchiectasis, the condition is as the critical factor in the pathogenesis of fundamentally the result of structural damage caused by bronchiectasis.44,45,46 In healthy individuals, a brief, prior bacterial or viral bronchial infection.37 controlled inflammatory response is generally successful in retrospective study of elderly individuals with the protecting against microorganisms that have entered the established diagnosis of bronchiectasis, prior infection upper and lower respiratory tract. In compromised hosts, was the common denominator.38 However, infection inflammatory defense mechanisms fail to eliminate such and/or obstruction remain the necessary antecedents of organisms, which then colonize the respiratory tract. In response, inflammation is intensified and becomes chronic. Powerful chemoattractants continue to recruit Clinical features
macrophages to the site of infection, releasing increasing Clinical findings in individuals with bronchiectasis are quantities of cytotoxic agents.47 In effective inflammatory characteristic, but not specific. Typically, bronchiectasis responses, these agents, called proteolytic enzymes, are follows a relapsing, remitting course. In contrast to neutralized by corresponding antiproteolytic agents, patients with classical COPD, bronchiectasis is not related to tobacco smoking. In contrast to studies of older inflammation persists, an ongoing chemical reaction patients with chronic bronchitis, in which the majority are ensues, resulting in progressive, irreversible damage to male, two-thirds of older bronchiectasis patients are both the bronchial wall and airway cilia.49 Significant female.60 As a result of complications associated with mucus hypersecretion and retention is a consequence of chronic infection, most bronchiectasis patients are underweight. Typical bronchiectasis patients exhibitsymptoms including: Airway obstruction and ciliary dysfunction
Airway obstruction develops when mucus plugging and
infection occur together in association with dysfunctional Clinically active bronchiectasis is characterized by cilia.51 In healthy individuals, airway secretions are the production and expectoration of large quantities cleared by several mechanisms, including the mucociliary of sputum. The volume of mucus hypersecretion is in escalator, cough, peristalsis, two-phase gas-liquid flow proportional to the extent of inflammatory damage to and alveolar clearance. Cilia lining the conducting both the secretory apparatus and the mucociliary airways move mucus cephalad into the central airways so that it can be swallowed or expectorated. The efficiencyof this complex mechanism is influenced by several Cough
factors, including the structure, number, movement, and Patients with bronchiectasis typically produce more coordination of the cilia present in the airways as well as than 100 ml of mucus daily; some more than 500 ml.
the amount, composition, and rheological properties of The effort to expectorate this mucus may result in persistent, sometimes convulsive coughing episodes.
Cough may be ineffective both because impaired In bronchiectasis, a generalized impairment of mucociliary apparatus fail to mobilize secretions to mucociliary clearance is present, either as a component of the central airways and because changes in the a pre-existing condition such as primary ciliary rheological properties of mucus make it difficult to dyskinesia, or as a result of chronic inflammation.53,54 Ciliary impairment occurs in both localized and diffusedisease. Mucus clearance is moderately to markedly Hemoptysis
Significant hemoptysis is a feature of advanced suggest that several factors are involved in causing bronchiectasis. In response to severe inflammatory damage to clearance mechanisms.56 It is well known that changes in the bronchial wall, the blood supply is excess neutrophil elastase and other toxic byproducts of the inflammatory process disrupt both the structure andfunction of airway cilia. In addition, certain colonized Rales
microorganisms release substances that damage host cilia There may be few auscultatory findings, or and reduce their motility.57 Further, those bacteria may be pronounced rales, rhonchi, and wheezing.
chemotactic for leucocytes, preventing the inflammatoryreaction from subsiding.58 Digital clubbing
Frequently, bronchiectasis patients exhibit bulbous Peribronchial fibrosis
swelling of the terminal phylanges of the fingers and Simultaneously, there is lysis of elastic tissue in the toes. This phenomenon is associated with the chronic bronchial walls, and thickening and fibrosis occur.
suppurative process and sometimes with arterial Multiple abcesses may develop in these peribronchial areas, contributing to excess tracheobronchial secretions,impaired mucociliary clearance and chronic infection.59 Respiratory insufficiency and congestive heart failure
Progressive respiratory insufficiency, congestive heartfailure, and sepsis are the most common causes of pulmonary-related death in patients with advanced treatment. Effectiveness of antibiotic therapy is further limited by increases in the variety and resistance of nosocomialorganisms in populations of immune-compromised patients. Pulmonary function tests (PFTs)
No specific pattern of pulmonary malfunction is evident Mucociliary stimulants
in bronchiectasis, but individual pulmonary function A variety of pharmaceutical agents have been prescribed as scores may reflect combinations of obstructive and adjunct therapies to enhance mucociliary clearance. Among restrictive pathology. In localized disease, functional them, dry powder mannitol may be beneficial.67 impairment is rare. In patients with significantatelectasis, pulmonary function test (PFT) results Mucolytic agents
indicate restrictive disease, including reduced vital Mucolytic agents have little or minimal effect on secretion capacity (VC), functional residual capacity (FRC), and total lung capacity (TLC). In diffuse disease, PFTs aresimilar to those found in other COPDs.
Steroids may be prescribed for exacerbations of
bronchiectasis, but their usefulness is unclear.69 Bronchiectasis is a serious, debilitating, and increasingly Bronchodilators
prevalent disease. New descriptive data and improved Bronchodilators are prescribed for selected bronchiectasis diagnostic techniques permit early recognition and accurate patients with concurrent reactive airway disease.70 diagnosis. Likewise, research has improved understanding ofthe etiology and pathophysiology of the condition, permitting Surgery
timely, effective therapeutic interventions. Previously, Although surgical resection is a controversial therapeutic bronchiectasis was viewed as an advanced stage in the natural intervention, it may be performed to treat localized progression of a variety of diseases and conditions. Currently, symptomatic bronchiectasis. In younger patients with however, data on the pathophysiology of bronchiectasis severe, generalized disease and respiratory failure, bilateral suggests that certain diseases and conditions, such as uncontrolled infection, cystic fibrosis, ciliary dyskinesia, andimmunological defects, are viewed more accurately as riskfactors rather than as of specific causes. The common Airway clearance therapy
denominator that unifies diseases and conditions associated The central role of retained secretions in initiating and with bronchiectasis is their ability to increase susceptibility to perpetuating the bronchiectatic process is supported by the classic vicious cycle of pulmonary infection. abundant research.72,73,74,75 Mucus hypersecretion is both thecause and the effect of the destructive events characterizing Patients with risk factors predisposing them to the bronchiectasis. Uncleared secretions nurture organisms that development of bronchiectasis require preventative trigger the vicious cycle of pulmonary infection, support strategies.62 In patients presenting with clinical evidence of chronic inflammation, and retain high concentrations of bronchiectasis, underlying pathologies must be identified to these cytotoxic byproducts. Also, mucus is the medium prevent disease progression. Although the etiology of transporting the chemicals that damage ciliary apparatus bronchiectasis is complex and varied, the components of and other components of the lung defense system. Excess treatment are well established. Appropriate physical and mucus not only facilitates destruction of clearance pharmocologic interventions must be implemented to control mechanisms; certain rheological alterations make the infection and disease progression, relieve bronchial mucus tenacious. Retained secretions further promote and obstruction, and improve ventilation and gas exchange.63,64,65 exacerbate bronchiectasis by obstructing airways andinterfering with ventilation and gas exchange. Antibiotics
Effective use of antibiotics, usually for acute exacerbations,
Today, with new understanding of the etiology and successfully prevents disease progression both by eliminating pathogenesis of bronchiectasis, treatment must focus upon or reducing bacteria populations and by decreasing harmful prevention or early intervention. With current knowledge of enzymes associated with the inflammatory response.66 Not all diseases and conditions that increase the risk of developing patients respond to antibiotics alone. Patients may be infected bronchiectasis, as well as awareness of dangers associated or colonized with antibiotic-resistant organisms, or have with excessive use of antibiotics, a new approach to therapy significant defects of the mucociliary apparatus, exuberant is indicated. Because bronchiectasis is a consequence of a inflammation, or advanced disease which confound antibiotic well-defined cascade of pathological events, it is imperative to prevent patients' initiation into the vicious cycle. If the suggested that bronchiectasis was a result of bronchial wall inflammation infectious cycle is already established, therapy should be and bronchial obstruction resulting from secretion retention. Oslerrecognized that conditions including suppurative pneumonias of childhood, chronic tuberculosis, and the aspiration of foreign bodieswere common antecedents of bronchiectasis. Osler W. The Principles With the implementation of aggressive, effective airway and Practice of Medicine. New York, NY, Appleton 1892 (Special clearance therapy, pathogenic microorganisms and Edition: Birmingham, AL, The Classics of Medicine Library. 1978, pp inflammatory byproducts are removed. Such therapy Among patients who died during the study period 1926-1938, mobilizes retained secretions, augments mucociliary bronchiectasis was listed as the primary cause of death in 78%, and as a transport, and enhances clearance of thick mucus.77 Because primary or secondary cause in 92%. Methodological and demographic bacterial colonization and irreversible damage from mucus factors notwithstanding, the figures are impressive. Perry KMA, King plugging occurs most frequently in the peripheral airways, DS, Bronchiectasis: a study of prognosis based on follow-up of 400patients. Am Rev Tuberc 1940; 41: 531-548.
it is important to utilize a modality that treats all regions of 10 Konietzko NFJ, Carton RW, Leroy EP. Causes of death in patients with the lungs and reliably mobilizes mucus from small as well bronchiectasis. Am Rev Respir Dis 1969; 100: 852-858.
11 In studies of mortality in bronchiectasis published in 1974 and 1981,the condition was listed as primary cause of death in some 10% of References
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27 Morehead RS. Bronchiectasis in bone marrow transplantation. Thorax 49 Bronchiectasis and other bronchial abnormalities. In: Fraser RS, Muller NL, Colman N, Pare PD, (eds), Diagnosis of Diseases of the Chest, 4th 28 Barker AF. Bronchiectasis. Semin Thorac Cardiovasc Surg 1995; 7: Ed., (WB Saunders, Philadelphia 1999), p. 2165.
50 Mysliwiec, op cite, (n.1). Sputum production in bronchiectasis varies 29 Smith IE, Flower CD. Review article: Imaging in bronchiectasis. Br J in quantity from 20-500 milliliters per day, but the majority of patients produce at least 100 ml. A minority of patients whose bronchiectasis is Erasmus JJ, McAdams HP, Farrell MA, Patz EF Jr. Pulmonary confined to the upper lobes, such as that due to Mycobacterium nontuberculosis mycobacterial infection: radiologic manifestations.
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31 Romano L, Padoan R, Romano C. Disseminated bronchiectasis and cystic 51 Warwick WJ, Mechanisms of mucous transport. Eur J Respir Dis 1983; fibrosis gene mutations. Eur Respir J 1997 10(6): 1380-1391.
32 Mason AC, Nakielna BE. Newly diagnosed cystic fibrosis in adults: 52 Houtmeyers, et al. op cite, (n. 36).
pattern and distribution of bronchiectasis in 12 cases. Clin Radiol 1999; Research suggests that, in a subgroup of patients, generalized impairment of mucociliary transport is a major factor in their eventual 33 Pignatti PF, Bombieri C, Marigo C, Benetazzo M, Luisetti M. Increased development of bronchiectasis. This subgroup includes patients with incidence of cystic fibrosis gene mutation in adults with disseminated congenital defects as well as patients acquiring widespread damage to their bronchiectasis. Hum Mol Genet 1995; 4(4): 635-639.
mucociliary systems early in life, possibly due to infections. In fact, for most bronchiectatic patients, local damage to the respiratory tract Bacteria frequently associated with bronchiectasis include epithelium or bronchial wall along with a local clearance defect (e.g. due Staphylococus aureus, Streptococcus pneumoniae, Klebsiella to infection) might be the cause of mucociliary transport defect. Camner P, pneumoniae, Mycobacterium tuberculosis, Mycobacterium avium- Mossberg B. Airway clearance mucus and mucociliary transport. In: intracellulare, Mycoplasma pneumoniae, and Bordatella species; viruses Moren F, Dolovich MB, Newhouse MT, Newman sp. (eds.) Aerosols in include human papillomavirus, latent adenovirus infection, influenza Medicine. Principles, Diagnosis, Therapy. (Elsevier, Amsterdam, 1993), viruses, herpes simplex, and measles viruses; frequently isolated fungi pp. 247-260. Abstracted in Houtmeyers, et al, op. cite, (n. 36).
include Histoplasma capsulatum, Pneumocystis carinii, and aspergillus.
54 In the study of Wills et al., sputum from patients with bronchiectasis Houtmeyers E, Gosselink R, Gayan-Ramirez G, Decramer M.
was transported slowly, at a mean rate of 15% of that of control mucus Regulation of mucociliary clearance in health and disease. Eur Respir J on the mucus-depleted bovine trachea. Results suggest a serious defect in the ciliary transportability of sputum unrelated to the presence of 37 Nicotra MB, et al, op cite, (n. 17).
infection, as neither the presence of purulence or Pseudomaonas 38 Ibid. Seventy-one of 86 patients who were reliable historians cited severe aeruginosa in the mucus influenced transportability. This study indicated infection prior to developing bronchiectasis. Although all subjects could that mucus retention is not simply due to a larger quantity of normal not be screened meticulously for genetic disease, only five of 38 patients mucus being produced, as sputum was transported more slowly than an with diffuse bronchiectasis demonstrated primary ciliary dyskinesia and equal quantity of control mucus. Wills PJ, Garcia-Suarez MJ, Rutman A, another five had some form of underlying mucous disorder. None had Wilson R, Cole PJ. The ciliary transportability of sputum is slow on the hypogammaglobulinemia or alpha -antitrypsin deficiency. mucus-depleted bovine trachea. Am J Respir Crit Care Med 1995; 151: Stockley RA. Bronchiectasis-new therapeutic approaches based on pathogenesis. Clin Chest Med. 1987; 8(3): 481-494.
Svartengren M, Mossberg B, Philipson K, Camner P. Mucociliary In 1950, Reid described three types of bronchiectasis: Fusiform clearance in relation to clinical features in patients with bronchiectasis.
(cylindrical), the most common type, refers to mildly enlarged bronchi Eur J Respir Dis 1986; 68: 267-278.
that fail to taper distally; varicose, in which bronchial walls appear For a detailed discussion of the pathophysiology of mucociliary beaded, because areas of dilation are mixed with areas of constriction; damage in bronchiectasis, see, inter alia, Houtmeyers, et al, op cite, (n.
and sacular (cystic) characterized by severe, irreversible ballooning of 36); Wilson R, Sykes DA, Currie D, Cole PJ. Beat frequency of cilia the bronchi peripherally, with or without air-fluid levels. Reid LM.
from sites of purulent infection. Thorax 1986; 41: 453-458; Currie DC, Reduction in bronchial subdivision in bronchiectasis. Thorax 1950; 5: Pavia D, Agnew JE, Lopez-Vidriero MT, Diamond PD, Cole PJ, Clarke SW. Impaired tracheobronchial clearance in bronchiectasis. Thorax Currie DC, Saverymuttu SH, Needham S, et al. Indium-labeled 57 Pseudomonas aeruginosae, Hemophilus influenzae, and Streptococcus granulocyte traffic to the respiratory tract of patients with bronchiectasis pneumoniae all release factors that slow ciliary beat; H influenza also producing purulent sputum daily. Thorax 1990 Jul; 45(7): 541-4.
produces a factor that may disrupt ciliated epithelium. Wilson, R, Roberts D, Cole PJ. Effect of bacterial products on human ciliary function in vitro.
Fahy, JV, Schuster A, Ueki I, Boushey HA, Nadel JA. Mucus hypersecretion in bronchiectasis. Am Rev Respir Dis 1992; 146: 1430- 59 Mazzocco M, Kirilloff L, Owens G, Rogers R. Chest percussion and postural drainage in patients with bronchiectasis. Chest 1985; 88: 360- 46 Nicotra MB. Bronchiectasis. Semin Respir Infect 1994; 9(1): 31-40.
47 Cytotoxic agents include proteases, collagenases, elastases, and other 60 In a 1995 retrospective study of 123 elderly bronchiectasis patients, 54% never smoked and 70% were female. Nicotra, op cite, (n. 17).
The balance between proteolytic and antiproteolytic secretions is 61 Houtmeyers, et al. op. cite, (n. 36 ).
important in determining the development and extent of airway damage.
Cole PJ, ed. Strategies for the Management of Chronic Bronchial This is exemplified by alpha1-antitrypsin deficiency, in which an Sepsis. (Oxford: Medicine Publishing Foundation, 1984.) 63 Mazzocco MC, Owens GR, Kirilloff LH, Rogers RM. Chest percussionand postural drainage in patients with bronchiectasis. Chest 1985; 88 (3):360-363.
64 Stockley RA, Bronchiectasis: new therapeutic approaches based onpathogenesis. Clin Chest Med 1987 8(3): 481-494.
65 Nicotra, op cite. (n. 17).
66 Ibid. 67 A recent study of the effect of inhaled dry powder mannitol on mucociliary clearance in bronchiectasis indicates that it may be a usefuladjuct to a regimen of airway clearance therapy. Daviskas E, AndersonSD, Eberl S, et al. Inhalation of dry powder mannitol improves clearanceof mucus in patients with bronchiectasis. Am J Respir Crit Care Med.
1999; 159: 1843-1848.
68 There is little data to support the usefulness of currently availablemucolytic agents in the treatment of bronchiectasis. N-Acetylcysteine maycause bronchospasm. The value of iodinated glycerol, though widely used,is unproven. However, preliminary results suggest that the recentlyavailable human deoxyribonuclease holds promise. Ibid. 69 A recent study evaluating the anti-inflammatory effects of inhaledfluticasone in bronchiectasis demonstrated no significant changes inspirometry, but notable reductions in sputum inflammatory indicies.
Tsang K, Ho PL, Lam WK, et al. Inhaled fluticasone reduces sputuminflammatory indices in severe bronchiectasis. Am J Respir Crit CareMed 1998; 158: 723-727. 70 Although the use of bronchodilators may be an attractive option in thetreatment of bronchiectasis, in many cases the airway obstruction is notreversible. In the presence of bronchospasm, the use of inhaled beta-adrenergic agonists may be of value in those patients who demonstrate aclear response. Nicotra, op cite, (n.17).
71 Frey HR, Russi EW. [Bronchiectasis: current aspects of an old disease].
Schweiz Med Wochenschr 1997; 8 (127): 219-230.
72 Houtmeyers, et al. op cite, (n. 36).
73 Reid LM. The pathology of obstructive and inflammatory airway diseases. Eur J Respir Dis 1986: 69 (Suppl 147): 26-37.
74 Cole, op cite, (n. 6).
75 Warwick WJ. Mechanisms of mucous transport. Eur J Respir Dis 1983;(Suppl 127): 162-167.
76 Stockley, op cite, (n. 64 ).
77 Hardy KA, A review of airway clearance: new techniques, indications,and recommendations. Respir Care 1994; 39(5): 440-455.
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Protocol used by Liang in Bear Lab - UNC at Chapel Hill Polyclonal antibody affinity purification The protocol is specific for Coronin 1B polyclonal antibody affinity purification, andthe purified antibody was named as 4245.Exp . Rabbits were immu-nized with a GST fusion protein containing the human Coronin 1B C-terminal region(394-489 amino acids) by Covance. Serum was affinity purifie