Foreign body aspiration into the respiratory tract and lungs can lead to many pulmonary diseases with a variety of clinical manifestations. The type of inhalation-associated pulmonary syndrome depends on the amount and nature of the inhalant, the duration of inhalation, and the host response. Dr. Ryu from the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, USA, and Dr. Xiaowen Hu from the Department of Respiratory Medicine, Anhui Provincial Hospital, China, recently published a review in the journal Chest detailing the diagnosis and clinical manifestations of inhalation-associated pulmonary syndromes.
Aspiration (misaspiration) is the entry of a foreign body into the airway and lungs through the larynx. Misaspiration is common and can occur in healthy individuals. Isotope studies have shown that close to half of healthy subjects aspirate pharyngeal secretions during sleep. Misaspiration often leads to the development of cough, but sometimes misaspiration is not accompanied by other definite clinical symptoms, leading to underdiagnosis and misdiagnosis of misaspiration.
Among the aspiration-related pulmonary syndromes, airway obstruction due to foreign body aspiration, aspiration chemical pneumonia, and aspiration pneumonia are common. And recent studies have identified more and more types of inhalation-associated pulmonary syndromes with a wide variety of clinical and imaging manifestations.
Table 1: Inhalation-associated pulmonary syndromes
Epidemiology
Inhalation-associated pulmonary syndrome can occur in all age groups from infancy to the elderly. However, specific inhalation-associated pulmonary syndromes often occur in specific age groups or in people with a combination of clinical inhalation risk factors. For example, foreign body aspiration occurs most frequently in children and the elderly, especially in those with a combination of abnormal psychoneurological status or impaired swallowing mechanisms.
Aspiration chemical pneumonia occurs in patients undergoing general anesthesia or with a decreased state of consciousness due to drug overdose, which often results in aspiration of large amounts of gastric contents due to reflux. Aspiration pneumonia occurs in older adults with comorbid chronic diseases who reside in nursing homes.
Risk factors
Common risk factors include decreased state of consciousness, impaired airway defense mechanisms, dysphagia, gastroesophageal reflux disease (GERD), and recurrent vomiting (Table 2).
Table 2: Risk factors for inhalation-associated pulmonary syndrome
Pathophysiology
When aspiration occurs in healthy individuals, the amount of aspiration is usually small and not accompanied by clinical sequelae.
In GERD patients, gastroduodenal reflux contents of gastric acid, pepsin and bile acids can directly damage the laryngeal mucosa and stimulate the sympathetic nerves innervating the larynx and trachea, leading to the development of airway hyperresponsiveness. Repeated, small amounts of refluxed gastric contents inhalation can lead to the development of chronic, non-severe lung injury, such as diffuse aspiration capillary bronchitis and chronic exogenous lipoid pneumonia.
Gastric acid aspiration can lead to the development of chemical damage to the airways and lung parenchyma, and the cascade inflammatory response secondary to this chemical damage can lead to the accumulation of inflammatory cells and the release of various inflammatory mediators. When large amounts of gastric acid are accidentally inhaled, this can lead to the development of acute lung injury with diffuse alveolar damage and progressive hypoxemia.
Aspiration of solid or semisolid substances into the airway can produce mechanical obstruction, leading to the development of acute respiratory distress or asphyxia (depending on the site of obstruction and the size of the foreign body). Sharp inorganic substances can cause direct damage to the airway. Organic substances, such as nuts or meat, can cause not only bronchial stenosis obstruction but also local granulomatous inflammatory reaction.
Small foreign bodies can be inhaled unconsciously when the patient is intoxicated or in a drug overdose state. If the foreign body persists in the airway, it can lead to the development of bronchial obstruction, resulting in persistent cough, recurrent obstructive pneumonia, and bronchiectasis.
In the past, the lungs were considered to be a sterile environment, but non-culture studies have confirmed the presence of a wide range of bacteria in the lungs of healthy subjects. The microbiota of the lungs are diverse and do not originate exclusively from the oral cavity. The inhalation of oral microorganisms into the lungs alters the original respiratory environment and host immune response, resulting in a change in the original lung microbiota.
Aspiration pneumonia is caused by the inhalation of oropharyngeal secretions containing pathogenic microorganisms. Oral pathogenic microorganisms colonize the lungs and tend to occur in older adults with comorbidities. This population tends to have decreased salivary clearance and a poor oral hygiene environment. Older adults also often have a cough reflex and decreased immune function, which can also contribute to the development of pneumonia after inhalation of pathogenic microorganisms.
Diagnostic evaluation
The diagnosis of inhalation-associated pulmonary syndrome requires a combination of the patient’s history, clinical symptoms, and imaging features. A commonly used test to assess a patient’s dysphagia is the swallowing function television radiography, which assesses the patient’s oral, pharyngeal, and esophageal function. Other tests include fiberoptic nasal endoscopy, motility testing, and upper gastrointestinal endoscopy.
Endoscopic biopsy and dynamic pH testing can help clarify the diagnosis of GERD. Laryngoscopy or bronchoscopy with direct visualization of the airway combined with pulmonary function test results can help clarify the diagnosis of aspiration-related airway disease. Clinical symptoms combined with imaging features help to clearly diagnose inhalation-associated parenchymal lung lesions such as aspiration chemical pneumonia, aspiration pneumonia, and exogenous lipid-like pneumonia.
In occult aspiration, a definitive diagnosis can sometimes be made by lung biopsy (e.g., biopsy finding foreign bodies or lipid macrophages).
Airway lesions
1. Vocal cord dysfunction
Several laryngeal symptoms are closely associated with the development of GERD, including chronic laryngitis, laryngospasm, vocal cord granuloma, and vocal cord dysfunction. Respiratory physicians often misdiagnose vocal fold dysfunction as asthma. Normally, the vocal folds are slightly abducted during inspiration and slightly constricted during expiration, while vocal fold dysfunction manifests as contradictory movements of the vocal folds.
Some vocal fold dysfunction is caused by psychological factors and some vocal fold dysfunction is caused by irritating factors (e.g., laryngopharyngeal reflux).
Because the laryngoscopic presentation of laryngopharyngeal reflux is often nonspecific, it is not clear whether GERD and the development of vocal fold dysfunction are truly related. The diagnosis of vocal fold dysfunction is based on the patient’s symptoms (abnormal breath sounds and dyspnea), laryngoscopic manifestations (paradoxical movements of the vocal folds) and abnormal flow volume ring manifestations. Treatment needs to be directed at the underlying cause of vocal fold dysfunction and supplemented with various supportive treatments.
2.Foreign body aspiration
Foreign body aspiration is likely to be life-threatening and occurs in children. Foreign body aspiration is rare in adults. Therefore, when adults present with respiratory disease, the possibility of foreign body aspiration is often missed, especially if the patient forgets the aspiration event or is unaware that it has occurred. Most aspirated foreign bodies in the airway are foods, most commonly nuts.
Most patients with foreign body aspiration present with a persistent cough with exertional dyspnea, chest pain, or hemoptysis. Some patients may present with recurrent episodes of pneumonia or persistent pulmonary infiltrates, while others may be misdiagnosed as asthma due to persistent wheezing. Foreign body aspiration is easily misdiagnosed because of its non-specific clinical presentation. When the symptoms of “asthma” or “pneumonia” do not improve after symptomatic treatment, the possibility of a foreign body in the airway should be considered.
Chest radiographs of foreign body aspiration are often suggestive of lobar (segmental) atelectasis or hyperventilation, but sometimes the chest radiograph can be normal. Chest CT scans suggest the presence of an endobronchial mass, which is sometimes misdiagnosed as an endobronchial malignancy. Imaging during expiration shows signs of air trapping in the involved lung segment (lobe).
When foreign body aspiration causes chronic bronchial obstruction, the imaging presentation often progresses from the initial obstructive pneumonia to a solid lung shadow with bronchodilation.
Bronchoscopy can provide a definitive diagnosis of foreign body aspiration by visualizing the obstructing foreign body. The foreign body can usually be removed by bronchoscopy. In rare cases, surgical intervention is required (e.g., in patients with central airway obstruction).
Pill aspiration is a specific type of foreign body aspiration due to the fact that some pills, e.g. potassium and iron preparations, can dissolve in the airway, causing airway inflammation and narrowing. When the medication is dissolved, bronchoscopy also fails to detect the inhaled foreign body.
Therefore, timely diagnosis of drug inhalation and timely bronchoscopy to remove the drug while performing bronchial lavage can minimize the adverse effects.
3.Bronchiectasis
Bronchiectasis refers to irreversible bronchial deformation and dilatation caused by the combined effect of bronchial obstruction and infection, resulting in structural damage to the bronchial wall. It has been suggested that 4-18% of non-cystic fibrosis bronchiectasis is due to aspiration (more common in children). However, these studies did not establish a causal relationship between aspiration and bronchiectasis.
One study, combining 24-hour ambulatory esophageal pH monitoring, upper gastrointestinal imaging, and the site of bronchiectasis, suggests that aspiration may be the cause of bronchiectasis. Nevertheless, it is necessary to conduct further studies to clarify the etiology of bronchiectasis in order to achieve the correct treatment.
4. Bronchospasm
In GERD patients, gastric acid aspiration can cause bronchospasm and cough. The incidence of GERD is higher in asthmatics compared to the general population. One study noted that GERD is the most common cause of refractory asthma. However, one study evaluated the role of acid-suppressing drugs (e.g., proton pump inhibitors) in the treatment of asthma and found that acid-suppressing therapy improved symptoms in asthmatics with clinical GERD symptoms, but appeared to be ineffective in asthmatics without clinical GERD symptoms, even in those with poorly controlled asthma symptoms.
5. Diffuse aspiration capillary bronchitis
Capillary bronchitis is defined as inflammation and fibrosis in the fine bronchi (internal diameter ≤2 mm). Aspiration is not considered to be a common cause of capillary bronchitis. Recent studies have shown that diffuse aspiration bronchiolitis can occur in adults without significant risk factors for misaspiration.
In the study by Barnes et al, four adult patients aged 41-59 years with persistent respiratory symptoms and diffuse pulmonary solid shadowing were definitively diagnosed with chronic occult diffuse aspiration bronchiolitis by surgical biopsy.
Three patients had a history of GERD, but only one patient had significant gastroesophageal reflux (GER) symptoms. High-resolution CT (HRCT) scans confirmed the presence of diffuse micronodular shadowing and dendritic signs in these patients (Figure 1), rather than aspiration pneumonia (diffuse patchy infiltrative shadowing). Recurrent episodes of insidious misaspiration may be associated with GER during sleep.
Figure 1, High-resolution CT (HRCT) of diffuse aspiration capillary bronchiolitis. HRCT of the chest shows small nodular shadows all over both lungs, more so in the right lung. The “bud sign” (indicated by the arrow) is seen in the peripheral area of the lung.
The diagnosis of diffuse aspiration bronchiolitis can be considered if lung biopsy, bronchoscopy, or surgery suggests granulomatous inflammation, multinucleated giant cells, and foreign body aspiration. Notably, pathologists often overlook inhaled foreign bodies in lung biopsy specimens, resulting in misdiagnosis.
Treatment of diffuse aspiration capillary bronchitis should focus on the etiology: GERD or dysphagia. For patients with diffuse aspiration bronchiectasis with GERD who have failed to respond to drug therapy and still have recurrent episodes, fundoplication may be considered.
6. Occlusive fine bronchiectasis syndrome
Lung transplantation is the accepted treatment option for patients with end-stage lung Occlusive bronchiectasis (BOS) occurs in lung transplant patients and is the leading cause of death in lung transplant patients.BOS is mainly characterized by persistent airflow limitation. Constriction of small airway dense fibrous scars is the histopathological cause of this airflow limitation.
The incidence of GER in lung transplant patients is high, and aspiration is an important cause of BOS progression. Lung transplant patients with combined inhalation-associated GERD have a poor clinical outcome, most likely due to repeated microbial inhalation.
It has been shown that after laparoscopic fundoplication in lung transplant patients with combined GERD, the rate of lung function decline in these patients was significantly reduced. Further studies are needed to assess the impact of GERD and aspiration on the clinical course and regression of lung transplant patients.
Parenchymal lung lesions
1. Inhalational chemical pneumonia
The two most common inhalation-associated pulmonary syndromes are aspiration chemical pneumonia and aspiration pneumonia. Aspiration chemical pneumonia is an acute lung injury resulting from inhalation of large amounts of acidic gastric contents. Aspiration chemical pneumonia occurs in patients with a decreased state of consciousness, such as those under sedation, general anesthesia, drug overdose, epilepsy, severe stroke, or traumatic brain injury.
Although inhalational chemical pneumonia starts as a result of chemical injury (associated with low pH), bacterial infections often develop later, especially when acid-suppressive therapy is given, such as proton pump inhibitors or enteral nutrition. Secondary intrapulmonary bacterial infection at a later stage promotes colonization of the lungs by stomach contents containing pathogenic bacteria.
Aspiration chemical pneumonia starts with acute cough, dyspnea, and wheezing after reflux aspiration of gastric contents. In the following hours, hypoxemia and hypotension develop and may even progress to acute respiratory distress syndrome (ARDS).
However, some patients are sometimes missed by health care providers, such as those undergoing general anesthesia, who simply present with new solid imaging changes and a decrease in oxygen saturation. After 24-48 hours of onset, patients with aspiration chemical pneumonia progress to a diffuse intrapulmonary solid image.
The diagnosis of aspiration chemical pneumonia is not difficult when a clear history of reflux and aspiration is present, combined with progressive clinical and imaging findings. However, even when a clear history of aspiration is present, it is not necessarily a case of aspiration chemical pneumonia. And when the history of inhalation is unclear, the diagnosis of aspiration chemical pneumonia depends on the findings of bronchoscopy or respiratory secretions: aspiration chemical pneumonia is considered if bile or particulate matter is present in the airways.
Gastric fluid-associated biomarkers, such as pepsin and lipophilic cells, can be used to detect respiratory secretions or bronchoalveolar lavage (BAL) specimens. However, the use of these biomarkers is still controversial, and no studies have been performed to confirm the diagnostic validity of these biomarkers.
In many cases, aspiration chemical pneumonia is diagnosed clinically on the basis of history (e.g., receiving general anesthesia), acutely progressive respiratory symptoms, diffuse solid pulmonary shadowing, and the exclusion of other possible pathologies.
Treatment of aspiration chemical pneumonia is primarily supportive and includes aspiration of the aspirate through bronchoscopy or aspiration of the aspirate while using a tracheal tube to protect the airway. Because gas exchange is often impaired in patients with aspiration chemical pneumonia, patients may be given oxygen and sometimes even require mechanical ventilation.
Prophylactic use of antimicrobials is generally not recommended unless there is evidence of infection. The role of hormones in the treatment of aspiration chemical pneumonia is still controversial.
2. Aspiration pneumonia
Aspiration pneumonia is caused by inhalation of oropharyngeal secretions containing pathogenic microorganisms and is a common cause of community-acquired and nosocomial pneumonia. In a multicenter study in Japan, 18% of patients with community-acquired pneumonia and hospital-acquired pneumonia had aspiration pneumonia. Inhalation risk factors combined with the presence of gravity-related solid shadows on chest CT scans were considered for the diagnosis of aspiration pneumonia.
Patients with aspiration-associated community-acquired pneumonia tend to be older, have more comorbidities, and have a higher mortality rate than those with non-aspiration-associated community-acquired pneumonia. The typical presentation is malaise with cough, sputum, dyspnea, and periodic fever (several days to weeks apart). Many patients will experience weight loss and anemia. Bronchopneumonia is often seen on chest radiographs (patchy shadows), mainly located in the middle and lower lungs. Those patients with a longer course of disease may show necrotizing pneumonia, lung abscesses, or even abscess thorax on imaging.
Many patients with community-acquired aspiration pneumonia have a mixture of anaerobic and aerobic bacteria, whereas patients with nosocomial-acquired aspiration pneumonia tend to have gram-negative bacillary infections, including Pseudomonas aeruginosa. The choice of antibiotic depends on the type of infection (community / nosocomial), the general condition of the patient, and the severity of the disease. Local antibiotic sensitivities also need to be considered when selecting antibiotics, given the emerging drug-resistant strains.
3. Exogenous lipoid pneumonia
Exogenous lipoid pneumonia is a rare disease that results from the inhalation of lipid-containing substances into the lungs. In contrast, “endogenous” lipoid pneumonia is a histopathologic injury caused by lipid accumulation in alveolar macrophages, often secondary to obstructive pneumonia.
Exogenous lipid-like pneumonia starts acutely when large amounts of petroleum-related products are inhaled (including accidental and occupational inhalation). Chronic exogenous lipid-like pneumonia is difficult to diagnose because the clinical presentation is often nonspecific and lacks a clear history of inhalation. Chronic exogenous lipoid pneumonia may result from repeated chronic inhalation of mineral oil or similar substances when administered orally or via intranasal drops.
Symptoms of exogenous lipid-like pneumonia are similar to other inhalation-associated pulmonary syndromes and include: cough, dyspnea, and occasional chest pain, but more than half of patients are asymptomatic.
The most common manifestations on HRCT include nodules, gross glassy shadows, solid lesions, and lobular septal thickening. the most specific manifestation on CT scan is the presence of fatty (dense) areas in solid lesions of nodules and masses, which resemble lung tumors (Figure 2).
Figure 2. HRCT of exogenous lipoid pneumonia. a: lung window of chest HRCT showing irregular solid shadows bilaterally. b: right lung solids with fatty shadows (indicated by arrows).
The diagnosis of exogenous lipid-like pneumonia is based on the features of the chest CT scan (nodular shadow containing fat) and a history of exposure to oily substances (most commonly mineral oil ingestion). Other diagnostic bases are sometimes needed. Histopathological evidence may be obtained by bronchoscopy or surgical biopsy to confirm the diagnosis.
Histologically, chronic exogenous lipid-like pneumonia often presents with a large number of lipid-filled (lipid vacuoles) alveolar macrophages, giant cell granulomas, inflammatory cell infiltrates, and extensive fibrosis.BAL cytology suggesting the presence of lipid-filled alveolar macrophages may also be considered exogenous lipid-like pneumonia, but this presentation is nonspecific and therefore still controversial.
In patients with exogenous lipid-like pneumonia, it is sufficient to discontinue exposure to oily substances. For patients with diffuse lung lesions, glucocorticoid therapy may be considered, but the efficacy is uncertain.
4. Interstitial lung disease
It has been pointed out that inhalation and the development of interstitial lung disease are also closely related, especially idiopathic pulmonary fibrosis (IPF), a fibrotic disease of the lung parenchyma that eventually progresses to respiratory failure. the incidence of GERD is higher in patients with IPF. In recent years, many scholars have suggested a potential causal relationship between GERD and IPF.
Savarion et al. showed that both proximal and distal esophageal gastric acid levels were significantly higher in patients with IPF compared to those without IPF. In addition, bile acid and pepsin levels were higher in the bronchial BAL of IPF patients compared to controls, suggesting the presence of gastric acid reflux in IPF patients. Raghu et al. found that the clinical course of four IPF patients with GERD treated with medication and/or surgery was significantly stable or improved over a 4-year follow-up period.
The international guidelines for the diagnosis and treatment of IPF published in 2011 recommend treatment of asymptomatic GERD in most patients with IPF, but the guidelines acknowledge that the quality of the evidence is not high.
During the clinical course of IPF, some patients present with an acute exacerbation of respiratory symptoms, combined with increased impaired gas exchange and additional pulmonary nodules. Such acute exacerbations of IPF often have no clear etiology (e.g., pneumonia, heart failure, pulmonary embolism) and are likely to progress to death. Occult aspiration of gastric contents is a possible mechanism for acute exacerbations of IPF.
Lee et al. showed that BAL pepsin levels were higher in patients with acutely exacerbated IPF compared to those with stable IPF, suggesting that crypt aspiration may play a role in the acute exacerbation of IPF patients.
GERD and inhalation may play a similar role in other interstitial lung diseases. One study noted a significant increase in the number of acidic and non-acidic GERs in patients with scleroderma who had comorbid interstitial lung disease. There was a positive correlation between the severity of interstitial lung disease (assessed by HRCT) and the number of refluxes.
Christmann et al. evaluated the literature on the association of GER and scleroderma and found that “aggressive” treatment of GER should be recommended for all patients with scleroderma-related interstitial lung disease. To date, however, there is no clear evidence that GERD treatment improves outcome in patients with scleroderma-related interstitial lung disease or IPF.
Conclusion
Inhalation can occur insidiously, causing a combination of pulmonary clinical symptoms. Combining the patient’s clinical history (including risk factors for misaspiration) with relevant clinical and imaging manifestations can help to correctly diagnose aspiration-associated pulmonary syndrome and avoid the occurrence of missed and misdiagnosis.