596 SECTION V Pediatric Critical Care Pulmonary 3 Suppression of humoral and cell mediated immunity by cyto toxic and suppressive therapy 4 Increased use of immunosuppressive drugs in patients with an[.]
596 S E C T I O N V Pediatric Critical Care: Pulmonary Suppression of humoral and cell-mediated immunity by cytotoxic and suppressive therapy Increased use of immunosuppressive drugs in patients with an organ transplant or collagen vascular disease An increasing number of patients with AIDS An increased number of invasive surgical procedures in hospitalized children, which create portals of entry for fungi19 Primary Pulmonary Fungi Fungi that cause primary pulmonary infection in otherwise healthy hosts are generally endemic mycoses found in a particular geographic distribution The four major mycoses in this group are histoplasmosis, blastomycosis, coccidiomycosis, and paracoccidiomycosis.161 Chemiluminescent DNA probes are available for identification of blastomycosis, coccidioidomycosis, and histoplasmosis We review these primary pulmonary mycoses in the following section but exclude paracoccidiomycosis because this infection occurs primarily in South America, Central America, and Mexico Consult up-to-date journal articles for information regarding paracoccidiomycosis infections Pathogenesis The dimorphic fungi cause infection following inhalation of spores (conidia) into the pulmonary system In the lower respiratory tract the conidia transform into the yeast phase, which is susceptible to phagocytosis by the pulmonary macrophages These yeast forms may persist in the nonimmune host As the yeastladen macrophages are transported via the lymphatics to the peribronchial and mediastinal lymph nodes, hematogenous dissemination may occur However, with the primary pulmonary infection in the immunocompetent host, extrapulmonary infection is rare Progressive primary pulmonary infection in the absence of host defenses (such as in a patient who is immunocompromised or an infant) may lead to seeding of extrapulmonary sites, dissemination, and death if left untreated Cellular immunity is the primary host defense against these deep mycoses, many of which are subclinical and require no therapy However, children with severe life-threatening infections should be treated (Table 52.7) Histoplasmosis Histoplasmosis is caused by Histoplasma capsulatum, which is endemic in the east-central United States, particularly the Mississippi and Ohio River valleys Primary pulmonary histoplasmosis is asymptomatic in more than 50% of patients Patients usually become ill weeks following exposure, manifesting influenza-like illness with fever, chills, myalgia, headache, and a nonproductive cough Occasionally, children have a skin rash, arthritis, and erythema nodosum The chest radiograph may show patchy areas of pneumonitis and prominent hilar adenopathy After exposure to an unusually heavy inoculum, a more diffuse pulmonary involvement may occur with extensive nodular infiltrates Children with this TABLE Antifungal Therapy 52.7 Drug Indications Route Side Effects AmB All life-threatening mycoses IV Fever, chills, nephrotoxicity, anemia, hypokalemia, thrombophlebitis AmB lipid complex, AmB cholesteryl sulfate, AmB liposomal Failure or intolerance to AmB, organ transplantation with renal insufficiency IV Same as AmB with decreased nephrotoxicity and infusion-related adverse events Ketoconazole Not indicated for acute treatment of severe invasive disease; alternative for mild blastomycosis, histoplasmosis, Candida, or coccidiomycosis PO Nausea, vomiting, hepatotoxicity, testosterone synthesis blockade Fluconazole Cryptococcus, Candida (question in critically ill), coccidiomycosis PO Nausea, vomiting, dizziness Itraconazole Nonlife-threatening blastomycosis, sporotrichosis, histoplasmosis, paracoccidioidomycosis PO Nausea, hypokalemia, edema, hypertension, adrenal insufficiency, epigastric pain Voriconazole Aspergillus and Cryptococcus, resistant Candida spp IV Visual changes, fever, nausea, vomiting, elevated liver enzymes Caspofungin Treatment for resistant Aspergillus and possible combination therapy for Candida and endemic mycoses IV Fever, phlebitis, nausea, headache, elevated liver enzymes Micafungin Candida and Aspergillus species IV Phlebitis, rash, abdominal discomfort, nausea, vomiting, diarrhea, hyperbilirubinemia Posaconazole Candida Aspergillus Zygomycetes PO Fever, headache, prolonged QT, elevated liver enzymes, renal impairment, increased midazolam levels if used together Anidulafungin Candida and Aspergillus IV Diarrhea and hypokalemia AmB, Amphotericin B; IV, intravenous; PO, by mouth CHAPTER 52 Pneumonitis and Interstitial Disease condition frequently have significant dyspnea and may progress to respiratory failure The chest radiograph often returns to normal after a primary pulmonary infection; however, a number of residual abnormalities may be seen, including multiple nodules with a dense core of calcium (a target lesion), scattered calcifications within lymph nodes, and occasionally small “buckshot” calcifications scattered throughout both lung fields.161 Diagnosis The skin test is of epidemiologic value but is useless in individual case diagnosis because a positive test indicates only prior exposure to this disease Neither are direct smears of the sputum helpful for diagnosis Most cases are recognized by serologic studies and include immunodiffusion (M and H bands) and complement fixation Unfortunately, the immune diffusion test is relatively insensitive, and a response may be delayed following a primary infection The complement fixation test is more sensitive but less specific.162 A titer of 1:32 or higher against the yeast antigen is diagnostic if the clinical picture suggests histoplasmosis Children with rapidly progressing pneumonia that is not responding to antibacterial antibiotic therapy or those in impending respiratory failure urgently need a diagnosis Invasive procedures such as BAL, diagnostic lung aspiration, or open-lung biopsy are necessary to obtain the required information Complications Disseminated histoplasmosis is a progressive extrapulmonary infection that occurs most frequently in children younger than years and in patients with altered cellular immunity.17,163 The clinical features of disseminated disease include fever, weight loss, hepatosplenomegaly, cough, diarrhea, gastrointestinal ulcers, and skin lesions Anemia, leukopenia, and thrombocytopenia may occur as a result of bone marrow involvement in young children and may lead to rapid death Chronic disseminated disease, which is uncommon and insidious, may present as a nonspecific afebrile illness without cough or radiographic abnormalities Occasionally, disseminated histoplasmosis presents as a localized infection involving the CNS Chorioretinitis and pleural effusion, along with isolated gastrointestinal findings involving terminal ileum, can occur Treatment The usual primary pulmonary infection requires no treatment Amphotericin B should be used for persons with a severe infection, especially if it is life-threatening or associated with respiratory failure Upon clinical improvement, itraconazole should be given to complete the course of therapy Chronic cavitary histoplasmosis can be treated with IV amphotericin B or a long-term course of oral itraconazole or ketoconazole Pericarditis therapy should include antiinflammatory agents such as indomethacin or aspirin Failure of pericarditis to improve with nonsteroidal antiinflammatory medication should not prevent the use of a brief course of steroids because steroid use does not appear to predispose to dissemination.164–168 Blastomycosis Blastomycosis is endemic to the southeastern region of the United States but extends northward along the western shores of Lake Michigan across to northern Wisconsin and Minnesota and into Canada An intimate exposure to an infected site is required for infection rather than the casual exposure often found with histoplasmosis 597 and coccidioidomycosis.169–171 Most pediatric cases of blastomycosis occur in older children and adolescents in rural areas The pathophysiology is similar to that of histoplasmosis The clinical course of primary pulmonary blastomycosis is variable The symptoms are similar to those of acute bacterial pneumonia and include high fever, cough with productive purulent sputum, occasional pleuritic chest pain, and myalgias Such symptoms generally last to weeks The chest radiograph frequently demonstrates patchy areas of alveolar consolidation affecting one or both lower lobes Pleural effusions and cavitation can occur but are unusual A rather dense lobar infiltrate similar to pneumococcal pneumonia is uncommon but occurs more frequently in pulmonary blastomycosis than with other pulmonary fungi Clearing of the chest x-ray film may take to months Blastomycosis is not always self-limited, and progressive pulmonary infection can occur with acute dissemination to distant sites In such instances the child remains febrile and toxic with quite rapid progression Diffuse pulmonary involvement with acute miliary spread can lead to rapid respiratory failure and radiographic findings of ARDS Children may have asymptomatic primary pulmonary blastomycosis that is diagnosed only with reactivation blastomycosis involving the skin, bones, or other distant organ sites Reactivation blastomycosis appears to be most common in the first or years immediately after the initial pulmonary infection and probably occurs in less than 5% of all infected patients A chronic form of pulmonary blastomycosis may occur in patients who have no significant history of acute pneumonia but present with respiratory symptoms that have persisted for weeks or months These persons have a chronic cough, productive sputum, nocturnal fevers, night sweats, weight loss, and dyspnea Chest radiographs in persons with chronic blastomycosis may reveal a single large mass, often perihilar in location A more common finding is a fibronodular infiltrate with small cavities and fibrosis radiating toward the hila Such findings mimic tuberculosis Diagnosis No reliable skin test exists for pulmonary blastomycosis Sputum and material aspirated from BAL, lung aspiration, skin, or bone lesions may be examined directly after potassium hydroxide digestion, and the pathognomonic yeast forms are identified Such positive direct smears provide a rapid, accurate, inexpensive test Serologic tests include immunodiffusion using purified antigen The complement fixation test is less sensitive and less specific than the immunodiffusion test.172 Most acute cases are diagnosed by direct sputum smears or from BAL Complications Patients whose illnesses are clinically similar to bacterial pneumonia frequently have a self-limited process Life-threatening progressive respiratory failure similar to ARDS can occur In such instances, diagnosis and therapy, including mechanical ventilation, must be initiated promptly Dissemination occurs only in the most severe cases.173,174 With dissemination, characteristic skin lesions (i.e., raised and crusted) may occur on the face and upper extremities In persons with disseminated disease, bone involvement often includes the spine, ribs, and skull Treatment Acute pulmonary blastomycosis does not require treatment in all cases Treatment with IV amphotericin should be given if the 598 S E C T I O N V Pediatric Critical Care: Pulmonary patient is severely ill or if progressive illness occurs Oral itraconazole and ketoconazole have been used for the treatment of chronic pulmonary blastomycosis (similar to tuberculosis) but should not be used for severe life-threatening infections.175,176 Coccidioidomycosis Coccidioidomycosis is a relatively common infection that occurs primarily in the southwestern United States Sixty percent of patients with primary pulmonary infection have no symptoms or minimal symptoms Children years old or younger have a higher frequency of progressive disease than older children and healthy adults The clinical course of coccidioidomycosis is a flulike illness usually associated with fever, cough, and chest pain There may be a transient maculopapular eruption similar to erythema nodosum in children Radiographic abnormalities range from hilar adenopathy to patchy infiltrates with pleural effusion Diagnosis Diagnostic studies include skin testing, which has some usefulness if the patient has compatible respiratory illness and a past negative skin test Direct smears of potassium hydroxide-digested sputum are helpful if characteristic spherules are found Antibody detection through complement fixation may be a useful measure of the severity of disease.174 In cases of suspected coccidioidal meningitis, complement fixation tests on cerebrospinal fluid should be obtained because many patients have a negative spinal fluid culture with positive complement fixation studies The use of chemiluminescent DNA probes may aid in rapid diagnosis Complications Complications include chronic progressive coccidioidal pneumonia, which is similar to tuberculosis but uncommon in pediatric patients Disseminated coccidioidomycosis does occur and is often accompanied by persistent fever and rapid progression, with development of meningitis, bony lesions, and skin and soft-tissue disease A fulminant primary miliary spread of disease with severe respiratory failure and diffuse lung involvement has been observed in patients with altered immune status The disseminated disease frequently has an insidious onset following the primary pulmonary infection by weeks The meninges are the most worrisome site of extrapulmonary involvement because coccidioidal meningitis requires intrathecal amphotericin B therapy, and cure is unlikely.177,178 Treatment If the infection causes prolonged fever, progressive pulmonary disease, significant mediastinal adenopathy, or disseminated lesions, antifungal therapy with amphotericin B should be initiated Ketoconazole has been used in skeletal, cutaneous, and other localized infections but not for meningitis Coccidiomeningitis is the most difficult complication of this disease to treat; it requires intrathecal and systemic therapy with amphotericin B.179–181 OPPORTUNISTIC PULMONARY MYCOSES Pulmonary Aspergillosis Invasive pulmonary aspergillosis occurs almost exclusively in immunocompromised patients.15,182–185 Despite treatment, unless the underlying immune defect is ameliorated, invasive pulmonary aspergillosis is often fatal Many cases are nosocomially acquired, usually in hospitals undergoing renovation or new construction.171 Children with hematologic malignancies (e.g., myelogenous and lymphocytic leukemia) or organ transplantation are at the highest risk for the development of invasive disease, presumably because of the abnormal immune cells and the cyclic neutropenia induced by repeated doses of chemotherapy Persons with heart and bone marrow transplants are at higher risk for aspergillosis infection than are those with kidney transplants Neutropenia is an important risk factor for the development of aspergillosis because both the absolute neutrophil count and the duration of neutropenia have been related to the incidence of infection Use of steroids and immunosuppressive drugs also appears to predispose to invasive aspergillosis.186 Immune and myelosuppressed patients exposed to heavy aerosol concentrations of aspergillosis spores have an increased chance of the development of invasive pneumonia Efforts should be made to eliminate the risk of airborne conidiospores in patient areas If such elimination is not possible, then susceptible patients should be moved away from areas of excavation or construction Clinical signs of invasive aspergillosis are nonspecific The usual presentation includes pulmonary infiltrates and fever that not respond to empiric antibacterial therapy Patients may exhibit dyspnea, a nonproductive cough, pleuritic chest pain, and pleural friction rubs Symptoms are usually difficult to identify in small children, and auscultatory changes are typically found only with advanced disease Hemoptysis is uncommon in children Diagnosis Radiographs of the chest reveal virtually any infiltrative pattern, including patchy infiltrates, necrotizing pneumonitis, miliary nodules, and lung abscesses Early findings may include a round, patchy pneumonia that progresses to a wedge-shaped density characteristic of pulmonary infarctions.187 Definitive diagnosis of invasive pulmonary aspergillosis requires histopathologic identification of fungus in tissue specimens Positive sputum cultures not prove the presence of invasive disease even in compromised hosts, although isolation should be taken seriously and multiple positive cultures should be considered strong evidence of fungal infection in patients whose immunity is compromised Serologic antibody tests have no value in the diagnosis of invasive aspergillosis In severely ill children, fiberoptic bronchoscopy with bronchial lavage is the initial diagnostic test of choice in patients with suspected pneumonitis If the results of fiberoptic bronchoscopy are nondiagnostic, a lung biopsy (open or needle) may be required, though not often done Enzyme immunoassay detecting galactomannan antigen, a constituent of the Aspergillus cell wall, may aid in the diagnosis The sensitivity and specificity of this test depend on many factors.188 This assay may be run on blood or BAL specimens; this, along with cultures and CT findings, may aid in the diagnosis of aspergillosis without requiring a biopsy specimen Complications Untreated invasive pulmonary aspergillosis is usually fatal in immunocompromised patients Fatality rates greater than 80% are reported; however, survival may improve if appropriate therapy is initiated early in the disease Death usually results from progressive pneumonitis, pulmonary infarction, and massive hemoptysis On rare occasions, endocarditis, osteomyelitis, meningitis, or infection of the eye or orbit occurs Treatment Therapy with voriconazole should be initiated early in the course of the disease Surgical resection is usually not indicated in the CHAPTER 52 Pneumonitis and Interstitial Disease treatment of critically ill patients with uncontrolled disease However, it may be considered in patients who have only partial response to antifungal therapy or with relapsing disease in a well-defined lung segment or in those identified with massive hemoptysis Early initiation of antifungal therapy is warranted when invasive aspergillosis is suspected while investigations are ongoing Alternative therapies—including liposomal amphotericin and fluconazole—are available, but voriconazole remains the preferred therapy An individualized approach is recommended for refractory disease and is best guided by an infectious disease specialist.189–192 Pulmonary Candidiasis Of all the opportunistic pulmonary mycoses, candidiasis may be the most difficult to diagnose and treat effectively because the Candida organism routinely colonizes the upper respiratory tract, resulting in positive cultures without significant disease The prevalence of Candida pneumonitis has increased remarkably in the past decades due to the increased use of broad-spectrum antibiotic therapy, immunosuppressive drugs, indwelling vascular lines, prosthetic devices, and organ transplantation Pathogenesis Pulmonary candidiasis may occur by hematogenous seeding of the lung parenchyma from a distal infected site or through the direct invasion of inhaled or aspirated organisms Candida acquired through the hematogenous route demonstrates pulmonary lesions that are diffuse, bilateral, and miliary The endobronchial form of infection does not have a significant interstitial component such as that seen with a hematogenous form The endobronchial form radiographically demonstrates pulmonary lesions that are small, asymmetric, patchy, and frequently found in the lower lobes Diagnosis There are no pathognomonic signs and symptoms of pulmonary candidiasis The diagnosis should be considered in an immunocompromised febrile patient with a pulmonary lesion, particularly if broad-spectrum antibiotics were used without a response Oral pharyngeal involvement (thrush) indicates that the patient is harboring the organism in an invasive stage Retinal lesions on ophthalmoscopic examination may help identify invasive Candida A cutaneous lesion often seen in persons with invasive Candida is a discrete erythematous papule with an erythematous halo The radiographic findings of Candida pneumonia are nonspecific Early in the course of infection, patients have normal chest radiographs The isolation of Candida in culture from an otherwise sterile body fluid or tissue and identification of the organism in a biopsy specimen are diagnostic of invasive Candida Serologic studies are of no diagnostic value Proof of Candida pneumonia requires tissue examination or evaluation of alveolar lavage or protected brush samples from bronchoscopy as direct evidence of tissue invasion If these studies fail to identify the disease process, the diagnosis of pulmonary candidiasis may be established with a lung biopsy Complications As with other mycoses, pulmonary candidiasis may be complicated by systemic dissemination affecting other organs Concomitant infection with other organisms, particularly bacteria, is not uncommon 599 Treatment Effective treatment includes correction of the patient’s immunosuppression in addition to administration of an echinocandin (caspofungin, micafungin, anidulafungin) Lipid formulation of amphotericin is effective but less desirable because of toxicity Fluconazole can be used as step-down therapy but should be guided by an infectious disease specialist.193 Pneumocystis jirovecii Pneumonia Pneumocystis jirovecii, which is probably a protozoan, produces a unique infection In the early stages of the infection with cysts, trophozoites are found distributed within the alveoli, most commonly adjacent to the alveolar septum Usually in this phase no clinical signs or symptoms are evident With extension of infection, the number of organisms increases and bilateral diffuse distribution occurs throughout the lungs Eventually, desquamation of the alveolar septal cells occurs, with subsequent phagocytosis of the organisms by the alveolar macrophages Minimal inflammation occurs in discrete areas of the alveolar septum at this stage of the disease, and a child may or may not be symptomatic Ultimately the alveolar septum becomes thickened with inflammatory cells, producing the clinical manifestations of childhood pneumocystosis.194 In the infantile form there is extensive involvement of alveolar septa with plasma cell and lymphocyte infiltration The normal septal thickness may be increased to 20 times, which results in occupation of much of the alveolus by the distended septum Clinical Features The three forms of disease patterns in pneumocystosis are the child/adult form, infantile form, and a more chronic fibrosing form observed in some HIV-infected patients.195 The typical child/adult type of pneumocystosis occurs in children beyond infancy who have congenital or acquired immunodeficiency disorders or malignancies and in organ transplant recipients.196–198 Clinical symptoms of pneumonitis include fever, cough, tachypnea, cyanosis, flaring of the nasal ala, and retractions Chest auscultation usually reveals no adventitious sounds until the terminal stage of infection, at which time bilateral crackles may be present The chest radiograph initially may be normal, and changes may be seen only late in the course of the disease.199 In the infantile form of pneumocystosis, symptoms often begin insidiously; presentations include poor feeding, failure to thrive, and diarrhea Increasing tachypnea may be detected, with respiratory rates frequently in the range of 80 to 120 breaths/min A dry, nonproductive cough with increased retractions and flaring of the nasal alae become prominent Diffuse crackles may be heard bilaterally on auscultation of the chest, and most infants remain afebrile The clinical course in neonates and infants may be quite rapid, with progressive cyanosis and death resulting from respiratory failure within days More commonly, however, the course extends over a period of several weeks, with a mortality rate varying from 20% to 50% without treatment.198,200 The chronic fibrosing type of Pneumocystis pneumonia identified in patients with HIV is associated with the presence of long-standing symptoms, localized radiologic changes, and interstitial fibrosis.195 Diagnosis A definitive diagnosis requires documentation of P jirovecii in lung tissue The standard surgical open-lung biopsy provides 600 S E C T I O N V Pediatric Critical Care: Pulmonary histologic details; however, the necessity for general anesthesia presents additional risk, particularly in the critically ill child Identification of the organism in sputum is sufficient for the diagnosis, but inducing and obtaining sputum in young children is often difficult In such cases, bronchoscopy should be considered.201 Fiberoptic bronchoscopy with BAL, although not achieving yields as high as open-lung biopsy, offers a useful and safe alternative to open-lung biopsy.9,10,29 Transthoracic percutaneous needle aspiration and thoracoscopy have been used successfully and can be performed without the use of a general anesthetic.202,203 However, pneumothorax can be expected in up to 30% of children Once a specimen is obtained, it can be stained with one of the array of preparations by which the organism can be confidently identified PCR techniques amplifying P jirovecii DNA have been shown to be sensitive Specific detection methods can be applied to BAL samples, sputum, and nasopharyngeal aspirates with success.204 Serum lactate dehydrogenase is usually elevated in patients with P jirovecii pneumonia and appears to be related to the degree of lung injury.205 The chest radiograph often may be normal early in the course of P jirovecii pneumonia However, as the disease progresses, the pattern demonstrates a diffuse bilateral alveolar disease process with hyperinflation and, eventually, development of air bronchograms The bilateral densities are frequently more intense in the middle and lower lung fields Only late in the course of disease the upper lung fields become involved Atypical lesions have been reported, including pneumonitis limited to lobar areas Pneumatoceles and pleural effusions have been reported.206 Complications P jirovecii usually remains localized to the lungs, even with extensive disease A disseminated form has been documented with recovery of the organism from extrapulmonary sites, including bone marrow, liver, and spleen Life-threatening complications that can arise in patients with P jirovecii pneumonitis include pneumothorax and pneumomediastinum Pneumothorax, both spontaneous and iatrogenic, occurs frequently in patients with P jirovecii pneumonitis Some evidence indicates that upper lobe predominance of pneumothorax may be more frequent in those previously treated with inhaled pentamidine Pneumomediastinum, with associated respiratory failure, may be noted in patients receiving assisted ventilation Treatment Therapy for P jirovecii should include specific anti-Pneumocystis chemotherapy, inhibition of the pulmonary inflammatory response, and enhancement of the immunologic status of the patient.207–212 Several drugs have been used for treatment of pneumocystosis (Table 52.8) Trimethoprim-sulfamethoxazole may be administered either orally or intravenously and is the drug of choice for treatment of this disease.3,180 The second most widely used drug for treatment of P jirovecii pneumonitis is pentamidine isethionate.211,212 Its effectiveness has been well documented over several years, but it has an increased number of undesirable adverse effects and treatment failures compared with trimethoprim-sulfamethoxazole.197 Secondary to the prevalence of sulfa allergy and therefore a need for an alternative therapy for P jirovecii, pneumonitis studies continue to find new medication regimens and new medications that may be used as alternatives to trimethoprim-sulfamethoxazole TABLE Pneumocystis carinii Pneumonitis Therapy 52.8 Drug Route Duration of Therapy (Days) TMP-SMX IV/PO 21 DOC Pentamidine isethionate IV 21 DOC TMP dapsone PO 21 Alternative Clindamycin primaquine PO 21 Alternative Atovaquone PO 21 Alternative Prednisone IV/PO 21 Adjunctive agent Comments DOC, Drug of choice; IV, intravenous; PO, by mouth; TMP-SMX, trimethoprim-sulfamethoxazole They all have their own side-effect profile and their own riskbenefit profile.213–215 Administration of a corticosteroid such as prednisone should occur at the initiation of specific antiPneumocystis therapy to improve survival and attenuate or prevent the initial decline in oxygenation In addition to the specific therapies, efforts should be made to reverse the immune dysfunction that allowed occurrence of P jirovecii (i.e., reduce or discontinue immunosuppressive medications) Chemical Pneumonitis A large number of chemical and physical agents may produce intense inflammation of the lower respiratory tract in children Chemical pneumonitis and/or pneumonia may be acquired in several different ways, such as by aspiration, inhalation, ingestion, or injection Aspiration Pneumonia Aspiration pneumonia is composed of a diverse group of disorders that have in common the soiling of the lower respiratory tract by foreign, nongaseous substances For purposes of this chapter, neither the solid foreign body nor the infectious component of aspiration is discussed Gastroesophageal reflux disease (GERD) has been defined as the retrograde passage of stomach contents into the esophagus This condition may be asymptomatic or associated with significant regurgitation and vomiting, esophagitis, failure to thrive, and anemia.216 Aspiration into the pulmonary tree can cause significant complications, including apnea, pulmonary fibrosis, severe necrotizing pneumonias, recurrent bronchospasm, and death Diminished lower esophageal sphincter pressure is often the result of physiologic immaturity; hence, GERD is more frequent in younger infants This disorder also occurs in older children, especially those with central nervous and neuromuscular dysfunction Other high-risk pediatric populations include patients with congenital abnormalities of the tracheal-bronchial tree and those with severe chronic pulmonary disease (Box 52.3) Pathophysiology The association of GERD and lung disease has been well documented; however, the actual cause and effect of the relationship has not been firmly established Massive aspiration of gastric fluid ... in the diagnosis The sensitivity and specificity of this test depend on many factors.188 This assay may be run on blood or BAL specimens; this, along with cultures and CT findings, may aid in... infection with cysts, trophozoites are found distributed within the alveoli, most commonly adjacent to the alveolar septum Usually in this phase no clinical signs or symptoms are evident With... discrete areas of the alveolar septum at this stage of the disease, and a child may or may not be symptomatic Ultimately the alveolar septum becomes thickened with inflammatory cells, producing