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Significant Aspirations: Recurrent Pneumonia

Published:September 17, 2013DOI:https://doi.org/10.1016/j.amjmed.2013.08.001

      Presentation

      The source of recurrent pneumonia was difficult to pinpoint in a 65-year-old white woman without typical risk factors. She presented to her primary physician with a productive cough, dyspnea, fever, and fatigue of 1-week duration. A former smoker, she had quit 25 years earlier. Her medical history was significant for hypothyroidism, gastroesophageal reflux, osteoporosis, fibromyalgia, and depression. Prior surgeries included gastric bypass surgery for obesity, cholecystectomy, hysterectomy, and breast reduction. She denied a history of seizure as well as alcohol, sedative or illicit drug use.
      Initial chest radiography was suggestive of right upper-lobe anterior segment pneumonia (Figure 1). She was treated with oral levofloxacin, but when repeat chest imaging revealed worsening opacities, she was hospitalized at another facility. During this time, her antibiotics were changed to vancomycin, ceftriaxone, and azithromycin. Computed tomography (CT) showed extensive pneumonic infiltrates in the right lung (Figure 2A). Bronchoscopy reportedly showed normal endobronchial anatomy and mucosa; bronchoalveolar lavage was unrevealing. She subsequently improved and was discharged home with a residual cough and supplemental oxygen due to desaturation with ambulation.
      Figure thumbnail gr1
      Figure 1Posteroanterior and lateral chest x-rays showed the opacity in the right upper-lobe anterior segment.
      Figure thumbnail gr2
      Figure 2Computed tomography (CT) of the chest was obtained. (A) An initial study demonstrated airspace opacities in the right lower and middle lobes—these produced air bronchograms. (B) A study obtained 3 months after the patient's initial chest CT disclosed scattered right lower- and middle-lobe airspace opacities with peripheral nodules suggestive of tree-in-bud pattern. (C) Five months after the first chest CT was obtained, another study revealed dense consolidation of the left upper and lower lobes. Resolving right upper-lobe disease also was seen. (D) Ten months after the initial chest CT, nearly complete resolution of the infiltrates was noted.
      Three months after her initial presentation she was referred to our institution for continued productive cough and persistent pneumonia. She reported mild weight gain and occasional night sweats but denied fever, chills, and chest pain. Repeat chest CT confirmed residual right-lung infiltration with a new subtle abnormality of the lingula (Figure 2B).

      Assessment

      The patient was afebrile and in no distress on ambient air. Physical examination and vital signs were remarkable only for auscultatory fine crackles at the right lung base and mild diffuse musculoskeletal tenderness.
      She had a normal leukocyte count and differential and an elevated sedimentation rate at 40 mm/hr (normal, 0-20 mm/hr). Histoplasma and Blastomyces complement fixation, urinary Legionella and pneumococcal antigen testing, and anti-nuclear and anti-neutrophilic cytoplasmic antibody levels were all negative. Results from serum IgE levels, a metabolic chemistry panel, and liver function and renal function tests were within normal limits.
      Transbronchial lung biopsy of the right upper lobe demonstrated a foreign body reaction consistent with chronic aspiration (Figure 3). A modified barium swallow test obtained after the biopsy was negative for both dysphagia and aspiration.
      Figure thumbnail gr3
      Figure 3A lung biopsy documented a foreign body reaction with amorphous material consistent with food particles (arrows) (hematoxylin and eosin stain, x200).
      The patient returned to clinic 2 months later with continued cough but no fever. She was referred for upper GI endoscopy, which disclosed a diaphragmatic hernia with normal esophageal mucosa. Three weeks later, she developed fever and brown sputum production and was once again hospitalized. Chest CT displayed a new extensive left-lung consolidation (Figure 2C). Laboratory testing detected an elevated leukocyte count with leftward shift. Repeat cultures and serologies were unrevealing. Bronchoscopy and transbronchial biopsy of the left lower lobe again showed pathologic findings consistent with chronic aspiration. Bronchoalveolar lavage with Oil Red O staining verified a lipid-laden macrophage index of 78; ≥ 50 is consistent with chronic aspiration.

      Diagnosis

      After a second lung biopsy confirmed the presence of foreign material, the patient was given a diagnosis of recurrent pneumonia due to occult gastric aspiration, a problem stemming from gastroesophageal reflux. Although a variety of conditions associated with recurrent pneumonia were initially considered, these were excluded by a combination of radiography, laboratory tests, lung pathology, and ultimately, by clinical course (Table).
      TableConditions Associated with Recurrent Pneumonia
      ConditionRadiographic FindingsMethod of Diagnosis
      Immunodeficiency states (eg, AIDS, hypogammaglobulinemia)Non-specific pneumonic opacitiesLaboratory testing
      Structural lung disease (eg, bronchiectasis, COPD)Variable depending on diseaseChest CT
      Endobronchial obstruction (eg, foreign body, neoplasm)Pneumonia recurs in same lung segment(s)Bronchoscopy
      Pulmonary sequestrationMost occur in lower lobes; always recur in same segmentAngiography demonstrating systemic arterial supply
      AspirationTypically occurs in dependent lung segments; may produce tree-in-bud opacitiesSwallowing studies; bronchoscopy; lung biopsy (see text)
      Bronchiolitis obliterans with organizing pneumoniaPersistent or migratory airspace opacitiesLung biopsy
      Pulmonary vasculitisMultifocal airspace disease, nodules, cavitary massesLaboratory testing; lung biopsy
      Chronic eosinophilic pneumoniaNon-specific airspace infiltration; may be peripherally predominantBronchoscopy with alveolar lavage; lung biopsy
      Chronic occult aspiration is an under-appreciated cause of pulmonary disease, usually occurring in the setting of advanced age, dysphagia, altered consciousness, and degenerative neurological disorders.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      • Marik P.E.
      Aspiration pneumonitis and aspiration pneumonia.
      • Franquet T.
      • Giménez A.
      • Rosón N.
      • Torrubia S.
      • Sabaté J.M.
      • Pérez C.
      Aspiration diseases: findings, pitfalls, and differential diagnosis.
      • Gleeson K.
      • Eggli D.F.
      • Maxwell S.L.
      Quantitative aspiration during sleep in normal subjects.
      • Adnet F.
      • Borron S.W.
      • Finot M.A.
      • Minadeo J.
      • Baud F.J.
      Relation of body position at the time of discovery with suspected aspiration pneumonia in poisoned comatose patients.
      However, this entity has been documented in previously healthy individuals without these predispositions.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      Our patient's case is noteworthy because of the absence of these risk factors, the atypical location of the infiltrates, and the biopsy confirmation on separate occasions.
      Aspiration-related lung disease encompasses several distinct syndromes, depending on the volume and nature of aspirated material, event chronicity, and host response to the insult.
      • Wynne J.W.
      • Modell J.H.
      Respiratory aspiration of stomach contents.
      Up to half of healthy subjects aspirate small amounts of oral secretions in their sleep; presumably most of these people never come to clinical attention because they possess adequate cough reflex and immune response.
      • Gleeson K.
      • Eggli D.F.
      • Maxwell S.L.
      Quantitative aspiration during sleep in normal subjects.
      Simple aspiration pneumonitis is produced when aspirated acidic stomach contents cause chemical injury to the lung parenchyma. Although gastric acid inhibits lung bacterial clearance, bacterial superinfection usually does not occur.
      • Marik P.E.
      Aspiration pneumonitis and aspiration pneumonia.
      • Rotta A.T.
      • Shiley K.T.
      • Davidson B.A.
      • Helinski J.D.
      • Russo T.A.
      • Knight P.R.
      Gastric acid and particulate aspiration injury inhibits pulmonary bacterial clearance.
      However, bacterial pneumonia can result; classically in alcoholics with poor nutrition and inadequate oral hygiene, which results in an increased burden of oral bacteria.
      • Marik P.E.
      Aspiration pneumonitis and aspiration pneumonia.
      • Wynne J.W.
      • Modell J.H.
      Respiratory aspiration of stomach contents.
      In such cases, lack of prompt treatment can lead to lung abscess and empyema.
      • Franquet T.
      • Giménez A.
      • Rosón N.
      • Torrubia S.
      • Sabaté J.M.
      • Pérez C.
      Aspiration diseases: findings, pitfalls, and differential diagnosis.
      Lastly, repeated aspiration of partially digested stomach contents can lead to a granulomatous foreign body reaction with associated bronchiolitis and alveolar organization.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      Diagnosis of occult aspiration can be challenging, as these patients commonly present with nonspecific complaints. Nonetheless, this diagnosis should be considered in the setting of recurrent respiratory complaints and persistent or migratory radiographic abnormalities. Factors suggesting this diagnosis include conditions producing dysphagia and/or aspiration; examples are esophageal disease, such as stricture or gastroesophageal reflux, and bariatric surgery.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      • Marumo K.
      • Homma S.
      • Fukuchi Y.
      Postgastrectomy aspiration pneumonia.
      Other predisposing factors include obesity, obstructive sleep apnea, neurologic conditions, illicit drug and alcohol use, and chronic pain treated with narcotics.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      • Marik P.E.
      Aspiration pneumonitis and aspiration pneumonia.
      Radiologic findings in patients with proven occult aspiration reveal nonspecific airspace disease with tree-in-bud appearance, similar to other bronchiolar diseases.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      • Franquet T.
      • Giménez A.
      • Rosón N.
      • Torrubia S.
      • Sabaté J.M.
      • Pérez C.
      Aspiration diseases: findings, pitfalls, and differential diagnosis.
      • Köksal D.
      • Ozkan B.
      • Simşek C.
      • Köksal A.S.
      • Ağaçkýran Y.
      • Saşmaz N.
      Lipid-laden alveolar macrophage index in sputum is not useful in the differential diagnosis of pulmonary symptoms secondary to gastroesophageal reflux.
      The posterior segment of the upper lobes and the superior segment of the lower lobes are most often involved, but other lung regions can be affected, depending on the position of the patient at the time of aspiration.
      • Franquet T.
      • Giménez A.
      • Rosón N.
      • Torrubia S.
      • Sabaté J.M.
      • Pérez C.
      Aspiration diseases: findings, pitfalls, and differential diagnosis.
      • Wynne J.W.
      • Modell J.H.
      Respiratory aspiration of stomach contents.
      • Marumo K.
      • Homma S.
      • Fukuchi Y.
      Postgastrectomy aspiration pneumonia.
      Lung biopsy, either surgical or bronchoscopic, can be diagnostic of aspiration when partially digested food particles with foreign body granulomas are discovered. This histopathological pattern also may include multinucleated giant cells, suppurative granulomas, and bronchiolitis with organizing pneumonia. Legumes, such as lentils, peas and beans, are the most often identified foreign matter.
      • Mukhopadhyay S.
      • Katzenstein A.L.
      Pulmonary disease due to aspiration of food and other particulate matter: a clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
      • Barnes T.W.
      • Vassallo R.
      • Tazelaar H.D.
      • Hartman T.E.
      • Ryu J.H.
      Diffuse bronchiolar disease due to chronic occult aspiration.
      • Marom E.M.
      • McAdams H.P.
      • Sporn T.A.
      • Goodman P.C.
      Lentil aspiration pneumonia: radiographic and CT findings.
      Other diagnostic modalities can increase clinical suspicion by documenting oropharyngeal dysphagia (eg, modified barium swallow test), esophageal pathology predisposing to aspiration (eg, upper gastrointestinal endoscopy), and proximal gastroesophageal reflux (eg, combined pH and impedance esophageal probe study), each of which increases the potential for occult aspiration. Yet none of these modalities has a well-documented sensitivity and specificity for confirmation of this diagnosis. In addition, although Oil Red O staining of bronchoscopically-obtained lavage cells has been advocated for diagnosing chronic aspiration, recent studies have been less promising.
      • Köksal D.
      • Ozkan B.
      • Simşek C.
      • Köksal A.S.
      • Ağaçkýran Y.
      • Saşmaz N.
      Lipid-laden alveolar macrophage index in sputum is not useful in the differential diagnosis of pulmonary symptoms secondary to gastroesophageal reflux.

      Management

      Therapy for this condition focuses on the prevention of aspiration, and where applicable, prevention of esophageal reflux. Depending on the patient's mechanism of disease, minimizing the use of sensorium-altering medications, swallowing rehabilitation, and alternative enteral nutrition (eg, tube feedings) may be useful.
      • Ney D.M.
      • Weiss J.M.
      • Kind A.J.
      • Robbins J.
      Senescent swallowing: impact, strategies, and interventions.
      Lifestyle interventions can reduce esophageal reflux—for example, patients can elevate the head of the bed during sleep, avoid the right lateral decubitus and recumbent positions for 3 hours after meals, give up smoking and alcohol, follow dietary restrictions, and lose weight if necessary.
      • DeVault K.R.
      • Castell D.O.
      Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease.
      Proton pump inhibitors are uniformly advocated for treatment of gastroesophageal reflux, but they do not prevent aspiration. Prokinetic medications, such as metoclopramide, are second-line agents that might benefit select patients. Surgical correction of pathologic reflux should be considered only in medically-refractory cases. Note, though, that no controlled trials have demonstrated efficacy in patients with lung disease caused by gastroesophageal reflux.
      Our patient improved with administration of broad-spectrum antibiotics, and she received detailed counseling on reflux prevention measures. During the subsequent year of follow-up, her chest CT cleared (Figure 2D). She had no further episodes of pneumonia.
      This case underscores the importance of recognizing the varied clinical and radiographic presentations of occult aspiration-related lung disease and the potential role of gastroesophageal reflux. Our patient's diagnosis was elusive due her lack of classic history and risk factors for recurrent aspiration and the atypical location of the radiographic opacities. After lung biopsy confirmation in each lung at different times, the diagnosis became completely clear, and only then was the significance of the prior bariatric surgery and gastroesophageal reflux understood. Ultimately, simple antireflux measures resulted in clinical and radiographic resolution.

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