601CHAPTER 52 Pneumonitis and Interstitial Disease produces direct injury to the mucosal surface of the respiratory tract, resulting in diffuse alveolar damage, hemorrhage, and nec rotizing bronchioli[.]
CHAPTER 52 Pneumonitis and Interstitial Disease • BOX 52.3 Pulmonary Aspiration and Gastroesophageal Reflux: Associated Disorders Associated Disorders • • • • Bronchopulmonary dysplasia Asthma Cystic fibrosis Infantile apnea Central Nervous System • • • • Convulsive disorders Anoxic encephalopathy Neurologic impairment Myopathies Congenital Malformations • Tracheoesophageal fistula • Hiatal hernia General • • • • Failure to thrive Achalasia Cardiopulmonary resuscitation Emergency surgery produces direct injury to the mucosal surface of the respiratory tract, resulting in diffuse alveolar damage, hemorrhage, and necrotizing bronchiolitis This may be followed by a rapid interstitial reaction, resulting in an acute inflammatory polymorphonuclear cell infiltration involving the interalveolar septa Bronchiolitis obliterans and fibrosis can occur In severe instances, the initial onset of disease closely resembles that of ARDS, with similar outcomes Repeated aspiration of small amounts of gastric contents may lead to recurrent pneumonia, airway hyperreactivity, bronchitis, and bronchiectasis with eventual fibrosis and involvement of the pulmonary interstitium Clinical Findings Clinical symptoms of GERD vary with age.216,217 In older children, heartburn, acid/bitter taste, retrosternal pain, or abdominal pain may be reported Infants may be irritable and exhibit stridor, poor sleeping patterns, or intermittent apnea Esophagitis can lead to microcytic anemia because of repeated episodes of gastrointestinal blood loss Chronic respiratory symptoms may include coughing, wheezing with choking episodes occasionally resulting in apnea, or life-threatening events similar to those seen in infants with sudden infant death syndrome In the hospitalized pediatric patient, significant aspirations may occur during or after general anesthesia Severe aspiration may be seen in patients receiving tube feedings as a result of displacement of the feeding catheter Findings on a chest radiograph may vary from slight hyperinflation to a pattern of diffuse interstitial and alveolar densities In mild cases, a picture of bilateral diffuse infiltrates compatible with ARDS may be seen Although a barium esophagogram can help to evaluate esophageal motility and detect esophagitis, it reflects only a single point in time Therefore, a negative study does not rule out the presence of GERD Radionuclide scans permit observation of esophageal function following the administration of a radioactive tracer Thus, the frequency and severity of reflux and information on esophageal and gastric dysmotility may be obtained If delayed aspiration occurs, the radionuclide may be 601 observed in the lung fields on a delayed scan.217 Esophageal motility and intraluminal pressures may be measured by esophageal manometry Intraesophageal pH measurement is helpful in that it allows long-term monitoring of acid reflux by detecting the frequency, duration, and intensity of reflux.218,219 Esophagoscopy is also useful for assessing the extent of mucosal injury by allowing direct visualization and obtaining a mucosal biopsy Use of BAL for assessment of lipid-laden macrophages has been useful in establishing or corroborating the diagnosis of aspiration in complex patients.218,219 Treatment Treatment of patients with GERD frequently includes placing the patient in an upright prone position and using thickened feedings Use of antacid preparations—omeprazole, cimetidine, ranitidine, and other inhibitors of H2 gastroreceptors—may be helpful in decreasing acid production and neutralizing its effects on the esophageal mucosa Omeprazole has, on rare occasions, been associated with electrolyte disturbances It has also been reported to possibly result in atrophic gastritis with prolonged use, but its use continues to increase despite these possible adverse effects.220–224 Metoclopramide is used before meals to help improve lower esophageal function and aid gastric emptying With the suspension of cisapride from the marketplace as an effective prokinetic agent because of potentially fatal toxicity, interest in erythromycin as a prokinetic agent has resurfaced Many trials evaluating its dose and efficacy are underway.225 Bronchodilators are used frequently to treat bronchospasm associated with GERD Because theophylline decreases the lower esophageal sphincter pressure, aerosolized b2-agonists are preferred In instances in which medical therapy was attempted and failed or in life-threatening situations, antireflux surgery is indicated In such instances, a fundoplication, partial plication, or percutaneous gastrojejunostomy is the appropriate treatment of choice.216 The most favorable outcome and lowest incidence of morbidity in such instances are achieved when surgery is delayed until the patient is adequately nourished and optimal pulmonary status has been obtained Inhalation Injury Acute inhalation injuries are a leading cause of fatalities in pediatric patients Smoke inhalation accounts for the largest number of pediatric lives lost to inhalation injury each year A significant number of inhalation injuries as a result of irritant gases occur through industrial or household accidents.226,227 Serious pulmonary inhalation injury may be manifested immediately or delayed in onset (Table 52.9).228–230 Pathogenesis Direct injury to the mucosal surface is the most common mode of pulmonary injury Inhalation of noxious substances may cause extensive physical damage to the lungs and seriously impair subsequent gas exchange The epithelial cells of air passages may become necrotic and desquamate, causing marked airway obstruction Bronchospasm caused by irritation from the inhaled gases or particles may lead to further airway obstruction Severe damage to the basement membrane may occur and cause subsequent leakage of intravascular fluid and blood into the alveolar and interstitial spaces Injury may occur at all levels of the respiratory tract depending on the physical and chemical properties of the irritant, the agent concentration, duration of exposure, and breathing pattern of the person exposed.228,231,232 The clinical course usually has 602 S E C T I O N V Pediatric Critical Care: Pulmonary TABLE Irritant Gases 52.9 Agent Exposure/Environment Direct Mucosal Injury Acrolein Plastic, rubber, textiles Ammonia Fertilizer, refrigerants, explosives Chlorine Bleaching, disinfectant Formaldehyde Disinfectant, paper, photography Hydrogen chloride Refining, dye making Hydrogen fluoride Etching, petroleum Nitrogen dioxide Welding, fertilizer, farming Phosgene Insecticide, dyes, chemicals Sulfur dioxide Bleaching, refrigeration Asphyxiation Injury Carbon dioxide Mining, foundry Carbon monoxide Smoke, foundry, mining Natural gas Mining, petroleum three phases: (1) the acute phase, which occurs within minutes or hours of the insult, resulting in pulmonary edema, hypoxemia, and respiratory failure; (2) the delayed phase, which occurs within the first few days and may include continuing effects of the lung injury, such as pulmonary edema, airway obstruction, and superinfection; and (3) the phase in which long-term sequelae may be noted because of the hypoxic or ischemic injury to other organ systems and recurrent pulmonary problems resulting from reactive airways disease or interstitial fibrosis Clinical Findings Clinical manifestations are nonspecific for inhalation of various irritant gases and may differ depending on the individual child Injury of the airways may be manifested as upper airway obstruction resulting in laryngotracheitis, bronchitis, and upper airway edema More peripheral airway obstruction may present with classic findings of asthma and airway edema with hypersecretion In cases of massive exposure, the presenting symptoms may be those associated with ARDS, manifested by profound V/Q mismatch, cyanosis, dyspnea, and respiratory failure Severe nasopharyngeal and laryngeal edema with hypersecretion may present as stridor.229,231 Chest radiograph findings are nonspecific, ranging from scattered areas of atelectasis and infiltrate to dense bilateral alveolar infiltrates Treatment Prompt physical removal from the offending agent and maintenance of upper airway patency are imperative Endotracheal intubation is a high-risk procedure; thus, meticulous attention must be directed toward maintaining proper pulmonary toilet and removal of upper airway secretions and debris from the artificial airway once it is secured Oxygenation should be monitored closely High oxygen concentrations, mechanical ventilation, and use of positive end-expiratory pressure may be necessary in the event of acute respiratory failure because the diminished compliance and formation of pulmonary edema occur rapidly Use of steroids may be justified in the treatment of patients who have been exposed to oxides of nitrogen; however, use after exposure to other irritant gases has not been validated Bronchoscopy may be indicated and useful in assessing the severity of airway injury and as an aid to endotracheal intubation and treatment of major areas of atelectasis However, use of BAL is usually not indicated except in instances in which significant particulate or carbonaceous material is likely Humidification of air and oxygen mixtures to thin secretions is necessary, and chest percussion/postural drainage may help to mechanically clear the airways Use of prophylactic antibiotics in persons with inhalation injuries is not recommended If pulmonary infection is suspected, prompt therapy with broad-spectrum antimicrobial agents should be started Use of bronchodilators is advocated because of a high incidence of bronchospasm No critical studies have evaluated this therapy in persons with an inhalation injury; however, the risk associated with its use is low, and administration to the child with obvious airflow obstruction is warranted Use of aerosolized b2-agonists is preferred Special attention is required in the presence of smoke inhalation with regard to the treatment of carbon monoxide poisoning Hyperbaric oxygen, if available, or sustained administration of 100% oxygen, is recommended in the initial treatment of patients with significant carbon monoxide intoxication Development of upper or lower airway edema may necessitate intubation and mechanical ventilatory support.228,232,233 Administration of artificial surfactant may be beneficial in patients in whom ARDS develops.233 Use of prophylactic steroids and antibiotics for persons affected by smoke inhalation is not recommended, especially if burn injuries are present, because complications are more frequent Prognosis The prognosis of children with acute pulmonary injury produced by inhalation of toxic gases is generally good Restrictive and obstructive pulmonary function abnormalities have been observed following recovery Residual defects such as bronchiolitis obliterans, bronchiectasis, and reactive airways disease have been observed following smoke inhalation Ingestion/Injection of Pharmacologic Agents Several chemotherapeutic agents and other commonly used drugs have potentially serious pulmonary toxicity (Box 52.4) Pulmonary toxicity is thought to be a direct effect in most instances, but immunologic and hypersensitivity mechanisms may also be involved Toxicity may occur during therapy or after discontinuation of the agent.234 The development of blebs in the capillary endothelium is followed by an interstitial fibrinous edema and mononuclear cell response with eventual hyaline membrane formation Some studies have shown a significant decrease in type pneumocytes with the evolution of type pneumocytes, septal thickening, and a proliferation of fibrous tissue with a decrease in the number of alveolar septa Pleural thickening may accompany the pneumonitis Diagnosis/Clinical Findings Characteristic clinical features of drug-induced pulmonary disease include fever, malaise, dyspnea, and a nonproductive cough Initial radiographic studies may be normal but usually demonstrate a diffuse alveolar and/or interstitial involvement Pulmonary CHAPTER 52 Pneumonitis and Interstitial Disease • BOX 52.4 Pharmacologic Agents Associated With Pulmonary Toxicity Cytotoxic Agents Antibiotics • Bleomycin: IP/PF, H, PEFF • Mitomycin C: IP/PF, PE, PEFF Alkylating Agents • • • • Cyclophosphamide: IP/PF, PE, B Busulfan: IP/PF, AH Chlorambucil: IP/PF Melphalan: IP/PF Antimetabolites • • • • Methotrexate: IP/PF, PE, H, PEFF Azathioprine: IP/PF G-mercaptopurine: IP/PF Cytosine arabinoside: IP/PF, PE Nitrosoureas • Carmustine: PF Noncytotoxic Agents • • • • • • • Amiodarone: IP/PF Carbamazepine: H, B Gold salts: IP/PF, H Nitrofurantoin: AH, PEFF, H, B, IP/PF Diphenylhydantoin: H Sulfasalazine: H, FA, BO, B Penicillamine: DA, AH, H, BO AH, Alveolar hemorrhage; B, bronchospasm; BO, bronchiolitis obliterans; DA, diffuse alveolitis; FA, fibrosing alveolitis; H, hypersensitivity lung reaction; IP, interstitial pneumonitis; PE, pulmonary edema; PEFF, pleural effusion; PF, pulmonary fibrosis function studies may be of either an obstructive or restrictive pattern Hypoxemia enhanced by exercise is an early and clinically important finding because interstitial pneumonitis and pulmonary fibrosis constitute a major portion of drug-induced pulmonary disease Histologic examination of lung tissue is frequently indicated to confirm the clinical diagnosis and to rule out other potential causes of pneumonitis, such as Pneumocystis, viral, or fungal infections that often occur in children treated with these agents Other complications—such as hypersensitivity lung disease, noncardiogenic pulmonary edema, bronchiolitis obliterans, alveolar hemorrhage, and pleural effusion—may occur in these patients Persistent and fatal lung dysfunction may follow druginduced pulmonary damage Therapy should be directed at early recognition of the problem, discontinuation of the offending agent, and supportive therapy Idiopathic Interstitial Lung Disease ILD of undetermined etiology is rare in adults but is even more uncommon in children Histologic classification of the idiopathic type of ILD can be somewhat confusing; in the past, pediatric classification mirrored the adult classification scheme As research progressed, some overlap was noted, but it was found that pediatric interstitial lung diseases have features that are unique to pediatrics Usual interstitial pneumonitis (UIP) has never been identified in children, as the diagnostic fibroblastic foci were not 603 found in any of the cases that had initially been labeled UIP Other interstitial pneumonias, such as desquamative interstitial pneumonitis (DIP) and lymphocytic interstitial pneumonia (LIP), are seen in children but remain quite rare and have some features that are different from their adult counterparts DIP in children is not associated with smoking Its histologic picture is one of macrophage being the primary inflammatory cell that fills the alveolus, although histiocytes, lymphocytes, eosinophils, and plasma cells are also present Hyaline membrane formation is not seen in DIP, and the structural integrity of the alveolar unit is usually maintained DIP tends to be responsive to steroids.233 LIP is seen mostly in patients with immune deficiencies and connective tissue disorders LIP tends to be insidious in onset and appears as a result of infiltration of the interstitium by plasma cells, mature lymphocytes, and histiocytes Nonspecific interstitial pneumonitis histologically is a mixture of inflammation and fibrosis This entity has been identified in children Cryptogenic organizing pneumonia has been identified in children as an isolated phenomenon or with infection, asthma, drug reactions, malignancies undergoing chemotherapy, bone marrow transplantation, and autoimmune disorders Prognosis is usually excellent, and patients have an excellent response to corticosteroids Acute interstitial pneumonia is a rapidly progressive disorder with a histologic appearance consistent with the organizing form of diffuse alveolar damage This diagnosis generally has a poor prognosis Some interstitial lung diseases that are unique to infancy were, in the past, most likely labeled under the aforementioned interstitial lung diseases but truly belonged in their own classification scheme These syndromes are persistent tachypnea of infancy (neuroendocrine cell hyperplasia of infancy), follicular bronchitis, cellular interstitial pneumonitis (pulmonary interstitial glycogenosis), chronic pneumonitis of infancy, and genetic abnormalities of surfactant function.235 Detailed discussions of these disorders of infancy or the other interstitial lung diseases and their management are beyond the scope of this chapter but can be found in various review articles.236–241 Patients who not respond to medical therapy should be considered candidates for lung transplantation Pediatric Pulmonary Hemorrhage Pulmonary hemorrhage (PH) is a potentially life-threatening event that can occur at any age The clinical presentation varies from massive fatal hemoptysis to silent bleeding with respiratory distress and anemia Rapid determination of the etiology of the PH and institution of a specific therapy is often difficult This section examines the less common causes of PH PH resulting from trauma and infection is not discussed Definition PH is defined as the extravasation of blood into airways and/or lung parenchyma Massive PH in adults is defined as blood loss of 600 mL or more in 24 hours.242–246 In infants, Esterly and Oppenheimer245 characterized massive PH as the involvement of at least two pulmonary lobes by confluent foci of extravasated erythrocytes Loss of 10% of a patient’s circulating blood volume into the lungs, regardless of age, causes a significant alteration in cardiorespiratory function and should be considered massive The diagnosis of PH following an episode of silent bleeding is established by pulmonary hemosiderosis, which is the abnormal accumulation of iron within lung parenchyma and alveolar macrophages 604 S E C T I O N V Pediatric Critical Care: Pulmonary Pathophysiology Accumulation of blood in the airways following a significant episode of PH creates multiple problems These problems include the production of a diffusion barrier resulting in hypoxemia and reduction in the diameter of involved airways, which, in turn, increases airway resistance and may lead to airway obstruction Reduction in pulmonary compliance and impairment of ventilation may occur.246–248 These changes in respiratory function increase both the ventilatory and myocardial work necessary to maintain a normal arterial oxygen tension Interstitial fibrosis that develops following repeated episodes of PH results in reduced carbon monoxide diffusion and diminished static and dynamic lung compliance Etiology Classification of the etiologies of PH provides a simple framework to proceed with diagnostic and therapeutic interventions (Box 52.5) Diffuse PH is usually associated with less total blood loss and can occur from either immune or nonimmune mechanisms Diffuse, immune PH typically affects adolescents and, less commonly, school-aged children Focal PH is commonly responsible for massive PH and carries a mortality rate greater than 50%.247,249–250 Focal PH typically affects preschool-aged children but may occur in infancy Diffuse/Nonimmune Pulmonary Hemorrhage PH in the neonate occurs in 0.7 to per 1000 live births and is present in 6% to 26.3% of neonates at postmortem examination Risk factors associated with PH in the neonate include asphyxia, infection/sepsis, CNS injury, weight less than 1500 g and/or smallfor-gestational-age, male sex, congenital heart disease, idiopathic • BOX 52.5 Causes of Pulmonary Hemorrhage Diffuse Nonimmune • Neonatal • Congenital heart disease • Hematologic respiratory distress syndrome, and coagulation disorders.250,251 Intraalveolar hemorrhage appears to occur more commonly in neonates of older gestational age PH in neonates as a primary occurrence is uncommon.250 Pathogenesis of PH in the neonate is considered to result from the development of persistent pulmonary hypertension with right-to-left intracardiac shunting of blood, resulting from hypoxia and acidosis Left ventricular failure ensues, causing an increase in pulmonary capillary pressure and subsequent disruption of pulmonary capillary and alveolar membranes Severe CNS injury may indirectly affect cardiac function, causing increased left ventricular end-diastolic pressure.252 Severe hemoptysis and life-threatening PH are rare in the preadolescent child with congenital heart disease However, a drastic increase in pulmonary capillary pressure in children with pulmonary atresia, unilateral pulmonary venous atresia, total anomalous pulmonary venous drainage with obstruction, mitral stenosis, cor triatriatum, or hypoplastic left heart syndrome may result in massive PH.252,253 Although the lungs are an infrequent site for early manifestations of primary bleeding disorders,243,246 a coagulopathy should be ruled out during the management of any patient with PH In patients with leukemia, PH occurs most frequently when the platelet count is lower than 10,000/mm Diffuse/Immune Pulmonary Hemorrhage The classic clinical triad of hemoptysis, microcytic hypochromic anemia, and diffuse alveolar-filling opacities on a chest radiograph (Fig 52.1) is found in most episodes of PH in this category Although the lung may be the only organ affected, more frequently, multiple organs are involved In patients with PH, establishing which extrapulmonary organs are involved by the disease helps to narrow the differential diagnosis of which of the immune-mediated disorders is most likely present Diffuse parenchymal bleeding without evidence of extrapulmonary involvement occurs in patients with idiopathic pulmonary hemosiderosis, Heiner syndrome, and drug-induced PH Idiopathic pulmonary hemosiderosis, a disease of childhood, is a diagnosis of exclusion Clinically, episodes of PH recur, with 30% to 50% of patients eventually dying of exsanguination and/or Immune • • • • • • • • • • • Lower respiratory and renal Goodpasture syndrome Idiopathic rapid progressive glomerulonephritis Upper and lower respiratory and renal Wegener granulomatosis Multisystem organ involvement Systemic lupus erythematosus Polyarteritis nodosa Behỗet syndrome Henoch-Schửnlein syndrome Rheumatoid arthritis Focal ã ã ã • • • Foreign body aspiration and chronic retention Sequestration Arteriovenous fistula Bronchogenic and gastroenteric cysts Thrombus or embolus Neoplasms: angiomas, adenomas • Fig 52.1 Chest radiograph of a patient with diffuse immune pulmonary hemorrhage CHAPTER 52 Pneumonitis and Interstitial Disease respiratory failure.254,255 Microscopic examination of the lungs is compatible with nonspecific injury rather than a specific cause such as vasculitis or immune deposits.254 Heiner syndrome, which affects children between the ages of months and years, usually manifests as other symptoms, such as chronic rhinitis, recurrent otitis media, and growth retardation.255 Tests for precipitating antibodies to milk proteins are positive Symptoms resolve when milk and milk products are eliminated from the diet Although uncommon, exposure to or inhalation of d-penicillamine, lymphangiography dye, trimellitic anhydride, cocaine, and exogenous surfactant256,257 has been associated with the development of PH Acute PH of an undetermined etiology occurring in infants has been reported.258,259 Idiopathic rapidly progressive glomerulonephritis is usually a disease of older adults (mean age, 55–60 years) In children with PH and either proteinuria, hematuria, or red cell casts, Goodpasture syndrome is the most likely etiology The presence of a linear immunofluorescent staining of Ig and C3 along glomerular capillary walls and antibasement membrane antibody (ABMA) in the serum confirms the diagnosis of Goodpasture syndrome Renal biopsy is the preferred primary method of confirming the diagnosis because an ABMA assay is not readily available at most institutions ABMA is a cytotoxic plasma Ig that reacts immunologically with components of alveolar and glomerular basement membrane Stress failure of pulmonary capillaries because of alteration of the alveolar and glomerular basement membrane may contribute to the likelihood of PH in these patients.260 Fifty percent of patients with Goodpasture syndrome die of asphyxia as a result of massive PH The presence of sinusitis and/or bilateral, multiple cavitary pulmonary nodules, and evidence of glomerulonephritis in patients with PH help distinguish Wegener granulomatosis from the other vasculitides.261 Serositis, arthritis, facial erythema, fever, and glomerulonephritis are present before the development of PH in patients with systemic lupus erythematosus (SLE).262 Ten percent of all cases of immune-mediated PH are associated with SLE.262 The onset of PH in patients with SLE is abrupt Pulmonary histology may or may not reveal a small vessel vasculitis characterized by neutrophilic infiltration of vessel walls and necrosis of capillaries and alveolar septa Renal histology shows a vasculitis represented by focal and segmental glomerulonephritis with absent or minimal immune deposits The majority of patients who have SLE and PH die.262 PH has been reported with most of the vasculitides, but the incidence is much lower than in the SLE population Constitutional signs and symptoms, such as musculoskeletal involvement, blood dyscrasias, and dermatitis, are the predominant clinical features of polyarteritis nodosa, the second most likely vasculitis-associated disease to cause PH.263,264 A segmental necrotizing (granular pattern) vasculitis is the characteristic lesion of polyarteritis nodosa, with PH a dominant feature.265 Recurrent uveitis, mucocutaneous ulcerations, and genital ulcerations in a patient with PH suggest Behỗet syndrome as the etiology Other clinical features seen with Behỗet syndrome include arthritis, gastrointestinal disease, cardiovascular involvement, and CNS disease.266,267 A necrotizing vasculitis of small to medium-sized arteries and veins and thromboses of the terminal vascular beds or vena cava confirm the diagnosis Although PH is an extremely rare complication of HenochSchönlein purpura or syndrome (when abdominal pain and arthritis precede the purpura), it should be treated aggressively because it may be fatal In a few patients with rheumatoid arthritis, syndromes resembling idiopathic pulmonary hemosiderosis without evidence of vasculitis or renal disease have developed 605 Focal Pulmonary Hemorrhage Congenital malformations that may be responsible for PH during infancy include angiomas and bronchogenic and gastroenteric cysts.249 Angiomas are located in the subglottic area and present with symptoms of airway obstruction by age months in almost 90% of cases Bronchogenic cysts arise from abnormal branching of the tracheobronchial tree, are lined with ciliated columnar epithelium, are filled with mucoid fluid, and, if they are in communication with the airway, they may demonstrate an air-fluid level They are prone to infection and may bleed if contiguous vessels erode Gastroenteric cysts, which are enteric duplication cysts lined with gastric mucosa, produce acid peptic secretions that may erode through adjacent vessels to cause bleeding Pulmonary sequestration, arteriovenous fistula, and bronchial adenomas are congenital malformations that may present in childhood or later life with PH With its tendency to become recurrently infected, a sequestered lobe may erode into its systemic arterial supply, causing massive PH.249 Pulmonary arteriovenous fistula with or without telangiectasia (isolated or familial) may produce massive PH during childhood, but this usually does not occur until adulthood.265,266,268 Adenomas are highly vascular tumors that, with minor trauma or inflammation, can cause PH Acquired causes of focal PH include aspiration of an organic foreign body and development of a pulmonary arterial thrombus or embolus.247 A patient presenting with PH and wheezing should lead the clinician to suspect a diagnosis of foreign body aspiration Prolonged retention of an organic foreign body leads to hyperplasia of tortuous bronchial vessels, varicosities, and bronchiectasis, any of which may cause PH Thrombi or emboli may develop in postoperative immobile children with central venous or pulmonary catheters, in female adolescents using oral contraceptives, or in patients with homozygous deficiency of antithrombin III, protein S, and protein C Focal PH may develop in children with cystic fibrosis as a result of bronchiectasis Treatment General The primary objectives in the treatment of PH are twofold: (1) to rapidly control the bleeding to prevent tissue hypoxia and/or ischemia resulting from airway obstruction and exsanguination and (2) to stabilize hemodynamics to prevent further damage to the kidneys or other extrapulmonary organs by the underlying disorder.244,267 Initial management of the patient with severe PH should occur in the setting of a critical care unit because of the potential lethality of this event (Box 52.6) General care measures include use of the Trendelenburg position as tolerated, oxygen supplementation, mechanical ventilation, and hemostasis therapy when indicated The Trendelenburg position may help clots propagate superiorly and exit the airway This position may not be well tolerated by patients with respiratory or cardiac embarrassment Positive end-expiratory pressure during mechanical ventilation may become necessary to reverse hypoxemia and may provide a measure of tamponade to the site of hemorrhage.244 Coagulation factors should be administered when indicated to lessen the severity of bleeding Hemodynamic monitoring with a pulmonary arterial catheter may be beneficial in some instances because high pulmonary artery occlusion pressure may worsen PH of any etiology Short-term control of bleeding may be obtained with insertion, under direct vision, of a balloon-tipped (Fogarty) catheter into the affected portion of the airway Right upper lobe ... acute phase, which occurs within minutes or hours of the insult, resulting in pulmonary edema, hypoxemia, and respiratory failure; (2) the delayed phase, which occurs within the first few days and... the evolution of type pneumocytes, septal thickening, and a proliferation of fibrous tissue with a decrease in the number of alveolar septa Pleural thickening may accompany the pneumonitis Diagnosis/Clinical... supportive therapy Idiopathic Interstitial Lung Disease ILD of undetermined etiology is rare in adults but is even more uncommon in children Histologic classification of the idiopathic type of ILD can