- Email: [email protected]
Bronchiectasis
P A R T 12 STRUCTURAL AND MECHANICAL ABNORMALITIES
CHAPTER
69
Bronchiectasis Marcus Herbert Jones and Paulo José Cauduro Marostica
TEACHING POINTS ● ● ● ● ● ● ●
Bronchiectasis should be suspected in children with chronic respiratory symptoms. A chest radiograph may not detect bronchiectasis. High-resolution computed tomography is the gold standard for the diagnosis of bronchiectasis. Cystic fibrosis should be considered in children with bronchiectasis. Postinfectious bronchiectasis is still frequent in developing countries. Antibiotics and chest physiotherapy are recommended by most experts. Patients with localized disease may benefit from surgery.
Bronchiectasis is a structural abnormality characterized by dilatation of the medium-sized bronchi. The usual clinical presentation is chronic productive cough and may lead to significant social and physical problems. Although bronchiectasis is observed in some congenital conditions, it usually occurs as a sequel to severe or repeated insults of respiratory infections or chronic aspiration. Bronchiectasis has been considered an irreversible abnormality. However, since high-resolution computed tomography (HRCT) has become available, some radiologically diagnosed cases in children were found to be reversible. 1 This is a challenge to the paradigm of a permanent finding suggesting that either different HRCT criteria for bronchiectasis in children should be used or this condition should be deemed as actually reversible in childhood. Most children with idiopathic bronchiectasis and those with nonprogressive causes have a good prognosis, with an almost normal life span, whereas those with background diseases like cystic fibrosis (CF) have a much worse prognosis, related to the progressive nature of the underlying illness.
EPIDEMIOLOGY Estimates of the prevalence of bronchiectasis are scarce. There are few reports of prevalence and incidence available, and further epidemiologic studies should be carried out to better assess the impact of this condition. The scarcity of prevalence studies reflects the lack of a noninvasive, simple, and accurate test that can be used in population investigations, so most diagnosed cases represent the more severe ones. 2-4
Although the prevalence of bronchiectasis is unknown, it seems to be higher in developing countries, where tuberculosis and childhood preventable diseases like pertussis and measles are still common. 3,5 In developed countries, the introduction of widespread immunization, improvement of social conditions, breastfeeding encouragement policies, and the access to antimicrobial therapy for tuberculosis and pneumonia have caused a decline in the incidence of bronchiectasis. However, bronchiectasis is still prevalent among indigenous peoples such as the Australian Aboriginal, 6 Alaskan, 7 Pacific and Maori children from New Zealand. 8,9 The prevalences reflect the socioeconomic conditions of a particular population. 4,10 At present, there has been a rise in tuberculosis rates directly related to the AIDS epidemic. This will cause an increase in the incidence of bronchiectasis, which will probably be diagnosed later during adulthood.
PATHOPHYSIOLOGY Usually a chronic or an intense insult, such as a severe viral infection, causes the initial lung damage, eventually leading to the emergence of bronchiectasis. Damage to the mucociliary clearance system evolves, leading to stasis of pulmonary secretions and further lung injury. There is a change in the epithelium from ciliated to cuboidal and squamous, reserve cell hyperplasia, and mucosal thickening. With progression, there is damage to the muscular and elastic layers. Inflammatory mediators and release of elastase from leukocytes lead to additional damage and eventual bronchial wall destruction with erosion of bronchial cartilage, especially in advanced saccular bronchiectasis. Elastase and cathepsin G are found in elevated concentrations in bronchoalveolar lavage fluid (BALF) from patients with bronchiectasis compared with normal controls, suggesting a decrease in downregulation of such enzymes by antiproteinases. Interleukin-8, a proinflammatory cytokine, is also overly expressed in BALF from patients with this disorder. 3 Once secondary infection is present, a cycle of infection and inflammation predisposes to further mucosal and bronchial wall injury 3,11,12 (Figs. 69-1 and 69-2). Localized bronchiectasis is usually related to a single bronchial obstruction, such as in foreign body aspiration or congenital malformations. In chronic cases, there may be vascular proliferation of the adjacent bronchial arteries that anastomose with pulmonary arteries and predispose the child to hemoptysis. 3
12 999
P A R T 12 ■ STRUCTURAL AND MECHANICAL ABNORMALITIES
Figure 69-1 Reserve cell hyperplasia, a dense mononuclear inflammatory infiltrate, and fibrosis. (Hematoxylin and eosin stain, original magnification ×100.)
Figure 69-3 HRCT scan of a 14-year-old cystic fibrosis patient showing cylindrical bronchiectasis in lower lobes.
Figure 69-2 The fibrotic area is stained in red, surrounding a bronchus with mononuclear infiltrate. (Verhoeff stain, original magnification ×100.)
Figure 69-4 HRCT scan of a 4-year-old patient with postinfectious bronchiolitis obliterans and localized cystic bronchiectasis in the right lower lobe.
The shape of the bronchiectasis is variable. The classic Reid classification 13 divides bronchiectasis into three different patterns: (1) cylindrical, where a uniform dilatation is found, (2) varicose, with constrictions superimposed on cylindrical bronchiectasis, and (3) cystic or saccular, where progressive dilation occurs, usually associated with more advanced disruption of the lung architecture, although such correlation is not always evident. 4 Figures 69-3 and 69-4 show the typical pattern of bronchiectasis on HRCT.
infection, immunodeficiency, congenital malformations, and aspiration syndromes. 11,14,15 Box 69-1 presents a list of known causes of bronchiectasis in children. In developing countries, infectious cases secondary to tuberculosis and pneumonia are still prevalent. In South America, postviral (especially adenovirus) bronchiolitis obliterans is a relatively common cause of bronchiectasis. 16,17 In a case-control study with Australian Aboriginal children, a strong and significant association was noted between hospitalized pneumonia and bronchiectasis, especially for recurrent and more severe pneumonia episodes with requirement for oxygen and longer hospital stays. 12 After the development of new antiviral drugs for the treatment of AIDS, vertically infected children are surviving longer and bronchiectasis is becoming a more frequent finding among such patients. Tuberculosis, lymphocytic interstitial pneumonia, and bacterial or Pneumocystis carinii pneumonia are frequently associated conditions with HIV-infected children. 18-20
CAUSES
12 1000
In many situations, bronchiectasis is secondary to a specific disease, but often no cause will be identified, despite a comprehensive etiologic investigation. In recently published series, 25% to 38% of pediatric patients did not have an identifiable underlying etiology for bronchiectasis. The most common causes in children include CF, severe respiratory
C H A P T E R 69 ■ Bronchiectasis
DIAGNOSTIC METHODS
BOX 69-1 Causes of Bronchiectasis in Children Infectious Bacterial pneumonia Pertussis Measles Adenovirus Influenza Tuberculosis Immunodeficiency Hypogammaglobulinemias Neutrophil deficiencies Complement deficiency AIDS Other Cystic fibrosis Primary ciliary dyskinesia Allergic bronchopulmonary aspergillosis Foreign body aspiration Aspiration syndromes Autoimmune diseases Young syndrome Mounier-Kuhn syndrome Ehlers-Danlos syndrome Marfan syndrome Yellow nail syndrome Alpha-1 anti-trypsin syndrome
Asthma itself is rarely, if ever, associated with bronchiectasis. In this situation, physicians should consider a different diagnosis or associated allergic bronchopulmonary aspergillosis or infection. 5,7,21 When localized disease is the case, one should consider an obstruction such as a foreign body or a congenital malformation. In cases of more diffuse disease, a systemic cause like CF, immunodeficiency, or primary ciliary dyskinesia is usually implicated. 5
CLINICAL FINDINGS Chronic respiratory complaints are the usual clinical findings. A productive cough is frequently present, and the association with wheezing or dyspnea often misleads physicians to the diagnosis of difficult asthma. As normal children often have respiratory tract infections, the presence of abundant sputum production may remain undetected, leading to diagnostic delay. Fetid sputum may also be present, although in the authors’ experience, it is only found, as is hemoptysis, in the more severely affected. Crackles and rhonchi are the usual auscultatory findings, more often detected during disease exacerbations. Digital clubbing is a variable finding, being reported in up to half of the patients, and does not necessarily correlate with severity of the disease. 9 There may be chest deformities. Malnutrition is frequently present in patients. 3,5,12,21-23
Bronchiectasis should be considered in all children with chronic respiratory symptoms, particularly if associated with a history of a severe respiratory infection in the past, digital clubbing, and malnutrition. HRCT of the chest has largely replaced bronchography for the diagnosis of bronchiectasis. It can accurately localize lesions, identify mucus plugging and bronchiolar abnormalities to the level of sixth-order bronchi and also identify focal areas of air trapping secondary to small airway disease. 11,21 Occasionally, bronchography is performed as a presurgical evaluation and when the diagnosis is uncertain. 24 Bronchography is associated with a risk of allergic reactions to the contrast media and with the possibility of ventilatory failure in patients who already have some degree of respiratory insufficiency. Most surgical series currently published do not mention bronchography as a mandatory preoperative test. 25 Ventilation-perfusion scintigraphy can be used to evaluate vascular perfusion and the extent of gas exchange in different areas. 26 Chest radiographs can be indicative of bronchiectasis, but they are not very sensitive. In the series by Eastham and coworkers, 22 66% of the HRCT diagnosed cases would have been missed by chest radiography alone; HRCT should be performed when the clinical picture is compatible, despite a normal chest radiograph. Usual radiographic findings are increased linear markings, the so-called tram lines, crowding of bronchi, cystic spaces, air-fluid levels, and honeycombing. 4,27 The standard HRCT technique is a thin section (1.0- to 1.5-mm collimation), at 10-mm intervals, with a highfrequency reconstruction algorithm. Usual window levels are −600 to −700 HU, and window width is 1000 to 1500 HU. 27,28 One of the classic signs of bronchiectasis in HRCT is a bronchial/adjacent pulmonary artery ratio greater than 1, which corresponds to bronchial dilatation; this is also known as the “signet ring” sign. It has been suggested that a 1.5 ratio should be used instead, because healthy people can have ratios as great as 1.5. Other classic signs include parallel bronchial walls that do not taper, the tram line appearance, or demonstration of bronchi in the peripheral third of the lung, mainly within 1 cm of the pleura. 4,11,28,29 In the retrospective series of bronchiectasis by Kang and coworkers, 28 87% of 47 resected lobes from adolescents and adults were correctly identified by the presurgical HRCT scans. Because all the patients had clinical indication for surgery, they probably represent the more symptomatic children. Areas of decreased attenuation can often be seen in HRCTs of patients with bronchiectasis. Pifferi and coworkers were able to identify attenuations in 37% of pulmonary lobes from 16 patients with bronchiectasis. 29 These areas correlated well with ventilatory and perfusional scintigraphy findings but did not necessarily correspond to the same areas where bronchiectatic changes could be observed. These changes could represent hemodynamic changes surrounding bronchiectasis. Pathologically, bronchiectasis consists of dilated bronchi, with inflammation and fibrous distortion of the bronchial wall, but biopsy specimens are not usually required, because image studies usually suffice for the diagnosis. 28
12 1001
P A R T 12 ■ STRUCTURAL AND MECHANICAL ABNORMALITIES
Interestingly, many cases of HRCT-diagnosed bronchiectasis have been demonstrated to be reversible. Either more strict criteria should be used to interpret HRCT in childhood, or some mild cases may actually be reversible. Gaillard and coworkers suggest that the persistence of clinical and CT findings for a period of 2 years is required to confirm the presence of true bronchiectasis. 1,22,30 Although some diseases can show a more frequent pattern of distribution of bronchiectatic lesions, none of the HRCT findings should be considered diagnostic, because there is great overlap. 4,11 In CF, upper lobe involvement is frequent, in contrast with other diseases where bronchiectasis tends to be more evident at other sites, especially in the lower lobes. 7,11,25 Aspiration typically causes more lower lobe bronchiectasis. In the series of Li and coworkers, 11 80% of such patients had bronchiectasis in the lower lobes. According to Hansel, 4 the middle lobe was more commonly involved in hypogammaglobulinemia. Li and coworkers 11 found a preponderance of lower and right middle lobe involvement in children with various types of immunodeficiency. Typical cases with an underlying cause such as CF, primary ciliary dyskinesia, or immunodeficiency usually show a multilobar involvement, in contrast to localized disease caused by infection. 5
MICROBIOLOGY Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus parainfluenzae, Staphylococcus aureus, and Pseudomonas spp. are the usual pathogens in children with bronchiectasis. 11,21-23 In CF, the most frequent bacteria are S. aureus, Pseudomonas aeruginosa, H. influenzae, and Burkholderia cepacia. 31
LUNG FUNCTION TESTS In non-CF patients, the correlation between bronchiectasis, assessed by an HRCT score, and lung function is weak. 32,33 Patients with bronchiectasis limited to a segment or lobe probably would have minimal abnormalities on spirometry. In CF patients, there is a mismatch between HRCT scores and spirometry, with a faster worsening of the bronchiectasis compared with lung function parameters. 34,35 However, some authors detected a moderate correlation between forced vital capacity (FVC) and forced expiratory volume is 1 second (FEV1) and HRCT scores in CF patients. 25,29,36 Children with bronchiectasis may have abnormal exercise with increased oxygen consumption and heart rates compared with controls, although exercise abnormalities have a poor correlation with HRCT scores or spirometry. 33
MANAGEMENT The management of bronchiectasis should focus on the care of the underlying condition, when this is the case, and the management of the suppurative lung injury itself. The former is beyond the scope of this chapter.
12 1002
Physiotherapy, one of the main treatments for CF patients, has not been appropriately evaluated for the care of non-CF bronchiectasis, but most experts recommend this therapy. No antibiotic strategies have been adequately evaluated with well-designed randomized controlled trials, mainly because bronchiectasis patients are not a homogeneous group and the studies that have been done are difficult to compare because of diverse study designs. 37 Infectious exacerbations should be treated with antibiotics. Some patients will need frequent courses of antibiotics for infection control. Some authors have suggested long-term antibiotic courses, aiming to reduce the bacterial population in order to avoid further inflammation and tissue destruction. 37 Inhaled tobramycin has been tried in adults with bronchiectasis infected with P. aeruginosa, and improvement in clinical outcomes was noted. 38 Although a safety study has already been conducted with inhaled gentamicin, the issue of its efficacy in children still needs to be addressed. 39 Macrolides have both an antimicrobial as well as anti-inflammatory and mucoregulatory effects. Different studies have shown the benefits of this class of drugs in patients with CF. Macrolides decrease interleukin-8 and neutrophil elastase in BALFs, improve spirometry parameters, and decrease the number of exacerbations and hospital admissions in most of the studies. 40 They are usually recommended in most centers for CF patients with moderate pulmonary involvement and especially for those chronically colonized by P. aeruginosa. In an uncontrolled study in adults, a decrease in pulmonary exacerbations and improvement in lung function in patients with non-CF bronchiectasis receiving azithromycin for a median period of 20 months was demonstrated. 41 Similar studies in children are needed to define the role of macrolides in nonCF bronchiectasis DNase, a mucolytic agent that causes lysis of DNA originating from bacteria and defense line cells, has been useful in the management of CF patients with bronchiectasis. However, it was found to be ineffective and potentially harmful in two studies of adults in stable condition with idiopathic bronchiectasis. 42,43 Surgery is usually indicated when adequate control is not achieved with clinical management. In adults, persistent symptoms following a 2-year treatment program is considered an indication for surgery, as is major hemoptysis. In children, social and general well-being issues, such as a failure to comply with a chest physiotherapy program, poverty, or failure to thrive, should be considered as possible indications for a surgical approach. 23,25,26 Good outcomes are obtained in children with localized disease, especially when there is no underlying disease that predisposes to new bronchiectasis formation and when all diseased segments can be resected. In one series, 44% of children eventually underwent surgery for localized disease. 15 Postoperative mortality is very low in most centers. 23,26
C H A P T E R 69 ■ Bronchiectasis
SUGGESTED READINGS Barker AF: Bronchiectasis. N Engl J Med 346:1383-1393, 2002. Callahan CW, Redding GJ: Bronchiectasis in children: Orphan disease or persistent problem? Pediatr Pulmonol 33:492-496, 2002. Chang AB, Masel JP, Boyce NC, et al: Non-CF bronchiectasis: Clinical and HRCT evaluation. Pediatr Pulmonol 35:477-483, 2003. Dagli E: Non cystic fibrosis bronchiectasis. Paediatr Respir Rev 1:6470, 2000. Eastham KM, Fall AJ, Mitchell L, et al: The need to redefine noncystic fibrosis bronchiectasis in childhood. Thorax 59:324-327, 2004.
Gaillard EA, Carty H, Heaf D, et al: Reversible bronchial dilatation in children: Comparison of serial high-resolution computer tomography scans of the lungs. Eur J Radiol 47:215-220, 2003. Karadag B, Karakoc F, Ersu R, et al: Non-cystic-fibrosis bronchiectasis in children: A persisting problem in developing countries. Respiration 72:233-238, 2005.
REFERENCES The references for this chapter can be found at www.pedrespmedtext.com.
12 1003
CHAPTER
69
Bronchiectasis Marcus Herbert Jones and Paulo José Cauduro Marostica
TEACHING POINTS ● ● ● ● ● ● ●
Bronchiectasis should be suspected in children with chronic respiratory symptoms. A chest radiograph may not detect bronchiectasis. High-resolution computed tomography is the gold standard for the diagnosis of bronchiectasis. Cystic fibrosis should be considered in children with bronchiectasis. Postinfectious bronchiectasis is still frequent in developing countries. Antibiotics and chest physiotherapy are recommended by most experts. Patients with localized disease may benefit from surgery.
Bronchiectasis is a structural abnormality characterized by dilatation of the medium-sized bronchi. The usual clinical presentation is chronic productive cough and may lead to significant social and physical problems. Although bronchiectasis is observed in some congenital conditions, it usually occurs as a sequel to severe or repeated insults of respiratory infections or chronic aspiration. Bronchiectasis has been considered an irreversible abnormality. However, since high-resolution computed tomography (HRCT) has become available, some radiologically diagnosed cases in children were found to be reversible. 1 This is a challenge to the paradigm of a permanent finding suggesting that either different HRCT criteria for bronchiectasis in children should be used or this condition should be deemed as actually reversible in childhood. Most children with idiopathic bronchiectasis and those with nonprogressive causes have a good prognosis, with an almost normal life span, whereas those with background diseases like cystic fibrosis (CF) have a much worse prognosis, related to the progressive nature of the underlying illness.
EPIDEMIOLOGY Estimates of the prevalence of bronchiectasis are scarce. There are few reports of prevalence and incidence available, and further epidemiologic studies should be carried out to better assess the impact of this condition. The scarcity of prevalence studies reflects the lack of a noninvasive, simple, and accurate test that can be used in population investigations, so most diagnosed cases represent the more severe ones. 2-4
Although the prevalence of bronchiectasis is unknown, it seems to be higher in developing countries, where tuberculosis and childhood preventable diseases like pertussis and measles are still common. 3,5 In developed countries, the introduction of widespread immunization, improvement of social conditions, breastfeeding encouragement policies, and the access to antimicrobial therapy for tuberculosis and pneumonia have caused a decline in the incidence of bronchiectasis. However, bronchiectasis is still prevalent among indigenous peoples such as the Australian Aboriginal, 6 Alaskan, 7 Pacific and Maori children from New Zealand. 8,9 The prevalences reflect the socioeconomic conditions of a particular population. 4,10 At present, there has been a rise in tuberculosis rates directly related to the AIDS epidemic. This will cause an increase in the incidence of bronchiectasis, which will probably be diagnosed later during adulthood.
PATHOPHYSIOLOGY Usually a chronic or an intense insult, such as a severe viral infection, causes the initial lung damage, eventually leading to the emergence of bronchiectasis. Damage to the mucociliary clearance system evolves, leading to stasis of pulmonary secretions and further lung injury. There is a change in the epithelium from ciliated to cuboidal and squamous, reserve cell hyperplasia, and mucosal thickening. With progression, there is damage to the muscular and elastic layers. Inflammatory mediators and release of elastase from leukocytes lead to additional damage and eventual bronchial wall destruction with erosion of bronchial cartilage, especially in advanced saccular bronchiectasis. Elastase and cathepsin G are found in elevated concentrations in bronchoalveolar lavage fluid (BALF) from patients with bronchiectasis compared with normal controls, suggesting a decrease in downregulation of such enzymes by antiproteinases. Interleukin-8, a proinflammatory cytokine, is also overly expressed in BALF from patients with this disorder. 3 Once secondary infection is present, a cycle of infection and inflammation predisposes to further mucosal and bronchial wall injury 3,11,12 (Figs. 69-1 and 69-2). Localized bronchiectasis is usually related to a single bronchial obstruction, such as in foreign body aspiration or congenital malformations. In chronic cases, there may be vascular proliferation of the adjacent bronchial arteries that anastomose with pulmonary arteries and predispose the child to hemoptysis. 3
12 999
P A R T 12 ■ STRUCTURAL AND MECHANICAL ABNORMALITIES
Figure 69-1 Reserve cell hyperplasia, a dense mononuclear inflammatory infiltrate, and fibrosis. (Hematoxylin and eosin stain, original magnification ×100.)
Figure 69-3 HRCT scan of a 14-year-old cystic fibrosis patient showing cylindrical bronchiectasis in lower lobes.
Figure 69-2 The fibrotic area is stained in red, surrounding a bronchus with mononuclear infiltrate. (Verhoeff stain, original magnification ×100.)
Figure 69-4 HRCT scan of a 4-year-old patient with postinfectious bronchiolitis obliterans and localized cystic bronchiectasis in the right lower lobe.
The shape of the bronchiectasis is variable. The classic Reid classification 13 divides bronchiectasis into three different patterns: (1) cylindrical, where a uniform dilatation is found, (2) varicose, with constrictions superimposed on cylindrical bronchiectasis, and (3) cystic or saccular, where progressive dilation occurs, usually associated with more advanced disruption of the lung architecture, although such correlation is not always evident. 4 Figures 69-3 and 69-4 show the typical pattern of bronchiectasis on HRCT.
infection, immunodeficiency, congenital malformations, and aspiration syndromes. 11,14,15 Box 69-1 presents a list of known causes of bronchiectasis in children. In developing countries, infectious cases secondary to tuberculosis and pneumonia are still prevalent. In South America, postviral (especially adenovirus) bronchiolitis obliterans is a relatively common cause of bronchiectasis. 16,17 In a case-control study with Australian Aboriginal children, a strong and significant association was noted between hospitalized pneumonia and bronchiectasis, especially for recurrent and more severe pneumonia episodes with requirement for oxygen and longer hospital stays. 12 After the development of new antiviral drugs for the treatment of AIDS, vertically infected children are surviving longer and bronchiectasis is becoming a more frequent finding among such patients. Tuberculosis, lymphocytic interstitial pneumonia, and bacterial or Pneumocystis carinii pneumonia are frequently associated conditions with HIV-infected children. 18-20
CAUSES
12 1000
In many situations, bronchiectasis is secondary to a specific disease, but often no cause will be identified, despite a comprehensive etiologic investigation. In recently published series, 25% to 38% of pediatric patients did not have an identifiable underlying etiology for bronchiectasis. The most common causes in children include CF, severe respiratory
C H A P T E R 69 ■ Bronchiectasis
DIAGNOSTIC METHODS
BOX 69-1 Causes of Bronchiectasis in Children Infectious Bacterial pneumonia Pertussis Measles Adenovirus Influenza Tuberculosis Immunodeficiency Hypogammaglobulinemias Neutrophil deficiencies Complement deficiency AIDS Other Cystic fibrosis Primary ciliary dyskinesia Allergic bronchopulmonary aspergillosis Foreign body aspiration Aspiration syndromes Autoimmune diseases Young syndrome Mounier-Kuhn syndrome Ehlers-Danlos syndrome Marfan syndrome Yellow nail syndrome Alpha-1 anti-trypsin syndrome
Asthma itself is rarely, if ever, associated with bronchiectasis. In this situation, physicians should consider a different diagnosis or associated allergic bronchopulmonary aspergillosis or infection. 5,7,21 When localized disease is the case, one should consider an obstruction such as a foreign body or a congenital malformation. In cases of more diffuse disease, a systemic cause like CF, immunodeficiency, or primary ciliary dyskinesia is usually implicated. 5
CLINICAL FINDINGS Chronic respiratory complaints are the usual clinical findings. A productive cough is frequently present, and the association with wheezing or dyspnea often misleads physicians to the diagnosis of difficult asthma. As normal children often have respiratory tract infections, the presence of abundant sputum production may remain undetected, leading to diagnostic delay. Fetid sputum may also be present, although in the authors’ experience, it is only found, as is hemoptysis, in the more severely affected. Crackles and rhonchi are the usual auscultatory findings, more often detected during disease exacerbations. Digital clubbing is a variable finding, being reported in up to half of the patients, and does not necessarily correlate with severity of the disease. 9 There may be chest deformities. Malnutrition is frequently present in patients. 3,5,12,21-23
Bronchiectasis should be considered in all children with chronic respiratory symptoms, particularly if associated with a history of a severe respiratory infection in the past, digital clubbing, and malnutrition. HRCT of the chest has largely replaced bronchography for the diagnosis of bronchiectasis. It can accurately localize lesions, identify mucus plugging and bronchiolar abnormalities to the level of sixth-order bronchi and also identify focal areas of air trapping secondary to small airway disease. 11,21 Occasionally, bronchography is performed as a presurgical evaluation and when the diagnosis is uncertain. 24 Bronchography is associated with a risk of allergic reactions to the contrast media and with the possibility of ventilatory failure in patients who already have some degree of respiratory insufficiency. Most surgical series currently published do not mention bronchography as a mandatory preoperative test. 25 Ventilation-perfusion scintigraphy can be used to evaluate vascular perfusion and the extent of gas exchange in different areas. 26 Chest radiographs can be indicative of bronchiectasis, but they are not very sensitive. In the series by Eastham and coworkers, 22 66% of the HRCT diagnosed cases would have been missed by chest radiography alone; HRCT should be performed when the clinical picture is compatible, despite a normal chest radiograph. Usual radiographic findings are increased linear markings, the so-called tram lines, crowding of bronchi, cystic spaces, air-fluid levels, and honeycombing. 4,27 The standard HRCT technique is a thin section (1.0- to 1.5-mm collimation), at 10-mm intervals, with a highfrequency reconstruction algorithm. Usual window levels are −600 to −700 HU, and window width is 1000 to 1500 HU. 27,28 One of the classic signs of bronchiectasis in HRCT is a bronchial/adjacent pulmonary artery ratio greater than 1, which corresponds to bronchial dilatation; this is also known as the “signet ring” sign. It has been suggested that a 1.5 ratio should be used instead, because healthy people can have ratios as great as 1.5. Other classic signs include parallel bronchial walls that do not taper, the tram line appearance, or demonstration of bronchi in the peripheral third of the lung, mainly within 1 cm of the pleura. 4,11,28,29 In the retrospective series of bronchiectasis by Kang and coworkers, 28 87% of 47 resected lobes from adolescents and adults were correctly identified by the presurgical HRCT scans. Because all the patients had clinical indication for surgery, they probably represent the more symptomatic children. Areas of decreased attenuation can often be seen in HRCTs of patients with bronchiectasis. Pifferi and coworkers were able to identify attenuations in 37% of pulmonary lobes from 16 patients with bronchiectasis. 29 These areas correlated well with ventilatory and perfusional scintigraphy findings but did not necessarily correspond to the same areas where bronchiectatic changes could be observed. These changes could represent hemodynamic changes surrounding bronchiectasis. Pathologically, bronchiectasis consists of dilated bronchi, with inflammation and fibrous distortion of the bronchial wall, but biopsy specimens are not usually required, because image studies usually suffice for the diagnosis. 28
12 1001
P A R T 12 ■ STRUCTURAL AND MECHANICAL ABNORMALITIES
Interestingly, many cases of HRCT-diagnosed bronchiectasis have been demonstrated to be reversible. Either more strict criteria should be used to interpret HRCT in childhood, or some mild cases may actually be reversible. Gaillard and coworkers suggest that the persistence of clinical and CT findings for a period of 2 years is required to confirm the presence of true bronchiectasis. 1,22,30 Although some diseases can show a more frequent pattern of distribution of bronchiectatic lesions, none of the HRCT findings should be considered diagnostic, because there is great overlap. 4,11 In CF, upper lobe involvement is frequent, in contrast with other diseases where bronchiectasis tends to be more evident at other sites, especially in the lower lobes. 7,11,25 Aspiration typically causes more lower lobe bronchiectasis. In the series of Li and coworkers, 11 80% of such patients had bronchiectasis in the lower lobes. According to Hansel, 4 the middle lobe was more commonly involved in hypogammaglobulinemia. Li and coworkers 11 found a preponderance of lower and right middle lobe involvement in children with various types of immunodeficiency. Typical cases with an underlying cause such as CF, primary ciliary dyskinesia, or immunodeficiency usually show a multilobar involvement, in contrast to localized disease caused by infection. 5
MICROBIOLOGY Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus parainfluenzae, Staphylococcus aureus, and Pseudomonas spp. are the usual pathogens in children with bronchiectasis. 11,21-23 In CF, the most frequent bacteria are S. aureus, Pseudomonas aeruginosa, H. influenzae, and Burkholderia cepacia. 31
LUNG FUNCTION TESTS In non-CF patients, the correlation between bronchiectasis, assessed by an HRCT score, and lung function is weak. 32,33 Patients with bronchiectasis limited to a segment or lobe probably would have minimal abnormalities on spirometry. In CF patients, there is a mismatch between HRCT scores and spirometry, with a faster worsening of the bronchiectasis compared with lung function parameters. 34,35 However, some authors detected a moderate correlation between forced vital capacity (FVC) and forced expiratory volume is 1 second (FEV1) and HRCT scores in CF patients. 25,29,36 Children with bronchiectasis may have abnormal exercise with increased oxygen consumption and heart rates compared with controls, although exercise abnormalities have a poor correlation with HRCT scores or spirometry. 33
MANAGEMENT The management of bronchiectasis should focus on the care of the underlying condition, when this is the case, and the management of the suppurative lung injury itself. The former is beyond the scope of this chapter.
12 1002
Physiotherapy, one of the main treatments for CF patients, has not been appropriately evaluated for the care of non-CF bronchiectasis, but most experts recommend this therapy. No antibiotic strategies have been adequately evaluated with well-designed randomized controlled trials, mainly because bronchiectasis patients are not a homogeneous group and the studies that have been done are difficult to compare because of diverse study designs. 37 Infectious exacerbations should be treated with antibiotics. Some patients will need frequent courses of antibiotics for infection control. Some authors have suggested long-term antibiotic courses, aiming to reduce the bacterial population in order to avoid further inflammation and tissue destruction. 37 Inhaled tobramycin has been tried in adults with bronchiectasis infected with P. aeruginosa, and improvement in clinical outcomes was noted. 38 Although a safety study has already been conducted with inhaled gentamicin, the issue of its efficacy in children still needs to be addressed. 39 Macrolides have both an antimicrobial as well as anti-inflammatory and mucoregulatory effects. Different studies have shown the benefits of this class of drugs in patients with CF. Macrolides decrease interleukin-8 and neutrophil elastase in BALFs, improve spirometry parameters, and decrease the number of exacerbations and hospital admissions in most of the studies. 40 They are usually recommended in most centers for CF patients with moderate pulmonary involvement and especially for those chronically colonized by P. aeruginosa. In an uncontrolled study in adults, a decrease in pulmonary exacerbations and improvement in lung function in patients with non-CF bronchiectasis receiving azithromycin for a median period of 20 months was demonstrated. 41 Similar studies in children are needed to define the role of macrolides in nonCF bronchiectasis DNase, a mucolytic agent that causes lysis of DNA originating from bacteria and defense line cells, has been useful in the management of CF patients with bronchiectasis. However, it was found to be ineffective and potentially harmful in two studies of adults in stable condition with idiopathic bronchiectasis. 42,43 Surgery is usually indicated when adequate control is not achieved with clinical management. In adults, persistent symptoms following a 2-year treatment program is considered an indication for surgery, as is major hemoptysis. In children, social and general well-being issues, such as a failure to comply with a chest physiotherapy program, poverty, or failure to thrive, should be considered as possible indications for a surgical approach. 23,25,26 Good outcomes are obtained in children with localized disease, especially when there is no underlying disease that predisposes to new bronchiectasis formation and when all diseased segments can be resected. In one series, 44% of children eventually underwent surgery for localized disease. 15 Postoperative mortality is very low in most centers. 23,26
C H A P T E R 69 ■ Bronchiectasis
SUGGESTED READINGS Barker AF: Bronchiectasis. N Engl J Med 346:1383-1393, 2002. Callahan CW, Redding GJ: Bronchiectasis in children: Orphan disease or persistent problem? Pediatr Pulmonol 33:492-496, 2002. Chang AB, Masel JP, Boyce NC, et al: Non-CF bronchiectasis: Clinical and HRCT evaluation. Pediatr Pulmonol 35:477-483, 2003. Dagli E: Non cystic fibrosis bronchiectasis. Paediatr Respir Rev 1:6470, 2000. Eastham KM, Fall AJ, Mitchell L, et al: The need to redefine noncystic fibrosis bronchiectasis in childhood. Thorax 59:324-327, 2004.
Gaillard EA, Carty H, Heaf D, et al: Reversible bronchial dilatation in children: Comparison of serial high-resolution computer tomography scans of the lungs. Eur J Radiol 47:215-220, 2003. Karadag B, Karakoc F, Ersu R, et al: Non-cystic-fibrosis bronchiectasis in children: A persisting problem in developing countries. Respiration 72:233-238, 2005.
REFERENCES The references for this chapter can be found at www.pedrespmedtext.com.
12 1003