Bagassosis

Etiology

Bagassosis is an airborne disease caused by inhalation of the fibrous cane-sugar residue, bagasse.[7] Chemically, bagasse is comprised of approximately 4% ash and 2% protein; the rest of the portion is made up of cellulose and various other complex plant carbohydrates. About one-half of the ash is made of silica.[8] 

Although bagassosis is caused by the inhalation of bagasse, the specific etiological mechanism responsible for causing the disease is considered multifactorial. Historically, the disease has been attributed to irritant properties of the bagasse itself, microorganisms present in the dust, its silica content, an allergic reaction, and a combination of these factors. It most commonly occurs in those frequently in contact with this material, e.g., sugar factory workers. A study showed that 11 out of 21 bagasse-shredding workers developed the disease over 15 months.[1] 

Aerobacter cloacae is a microorganism that has been seen as a possible causative organism in the etiology of bagassosis.[9] Most notably, thermophilic actinomycetes (T. sacchari and T. vulgaris) are the causative agents found in bagasse responsible for triggering a pathological response.[1]

Epidemiology

There is no mention of the prevalence of bagassosis in recent literature, and its sex and age distribution are unknown. It is a relatively rare disease, first described in 1941. Most of the initially reported cases were in southern American states, especially Louisiana. Few cases were reported in Europe and Asia.[1] Four reported cases came from a London factory in 1942. By 1958, the total number of cases reported globally in the literature was nearing 60.[1] However, after 69 cases occurred in 140 Puerto Rican paper-mill workers in 1960, the disease was no longer regarded as very uncommon.[1] 

Recent studies in India indicate clinically significant thermophilic actinomycetes are widely present in cane sugar mills, and Thermoactinomyces sacchari and Saccharopolyspora rectivirgula are the major species responsible for the sensitization of Indian bagasse workers.[10] A study carried out in Australia in 2010 revealed no evidence to believe the development of chronic bagassosis among the workers of the sugar industry. Therefore, there was no significant prevalence of bagassosis among bagasse workers in Australia.

Pathophysiology

Generally, hypersensitivity pneumonitis (HP) is thought to develop from the response of susceptible individuals to inhaled antigens leading to immunologically-induced parenchymal inflammation.[11][12] Bagassosis is an airborne disease caused by inhalation of the bagasse dust contaminated by thermophilic actinomycetes, most importantly, Thermoactinomycetes vulgaris.[7] This organism produces a hypersensitivity reaction characterized by widespread bronchoconstriction in the peripheral bronchopulmonary tree, resembling other extrinsic allergic alveolitis such as the farmer's lungs.[1][7]

However, other mechanisms have also been postulated in the pathophysiology of the disease, including the irritant property of bagasse itself, its silica content, other micro-organisms including fungi, or a combination of these factors.[13] In acute bagassosis, immune complexes mediate lung inflammation as evidenced by:

• Raised serum levels of antigen-specific immunoglobulin G (IgG)
• Elevated neutrophils in the lungs primed for enhanced respiratory response

In subacute and chronic bagassosis, characteristic T-lymphocytic alveolitis is noted, attributable to increased T-cell migration, decreased apoptosis, and local proliferation. Immune processes leading to persistent disease and fibrotic changes are unclear but may be mediated by:

• Raised CD4:CD8 ratio
• Reduced effector CD8 T cells
• Skewing toward T helper cell differentiation and cytokine profile

Histopathology

Bronchoalveolar lavage specimens from patients suffering from bagassosis show hypercellularity and neutrophilia.[14] Other findings include increased levels of TNF-alpha, IL-1beta, IL-8, and IL-6.[14] A lung autopsy shows minute needle-like spicules in the pulmonary tissue. When rotated in polarized light, these spicules have the same semblance and characteristics as bagasse fiber. Other findings are the presence of large cells with a foamy cytoplasm in the alveolar spaces and an interstitial fibroblastic tissue reaction.[13]

History and Physical

The onset of the disease may be acute or insidious. The acute onset is usually after exposure to a very large concentration of bagasse dust. In other cases, symptoms start to appear about four months to 12 years after exposure to the dust.[1] Classical presenting complaints include worsening and severe shortness of breath, cough, fever, malaise, and weight loss.[1][7] Acute illness develops within hours of exposure and may present with flu-like symptoms, such as fever, malaise, chills, cough, dyspnea, chest tightness, and headache. Symptoms gradually resolve within 12 hours to several days after removing the exposure, although they may recur following re-exposure.

Physical examination of patients with bagassosis reveals crepitations, which are generally basal but could be generalized in severe cases.[7] Findings vary according to clinical presentation, such as in patients with acute disease; the usual presenting features are fever, tachypnea, and fine bibasilar crackles on auscultation. Patients with subacute bagassosis present similarly, but symptoms are generally not as severe and have lasted longer. Patients with chronic disease may demonstrate muscle wasting and weight loss. Almost half of the patients would have clubbing. These patients also have respiratory distress, tachypnea, and inspiratory crackles.

Acute illness in the background of chronic bagassosis is usually severe and often presents with respiratory distress needing ventilation assistance.

The diagnosis is clinical and based on a positive occupational history, characteristic clinical features, and chest X-ray findings, and after the exclusion of other possible conditions.[13]

Evaluation

Blood tests are usually unremarkable; normal white cell counts, normal PCO2, and slightly elevated ESR.[1] The chest X-ray shows fine micronodular shadowing but may be normal in some patients. Pulmonary function tests show a restrictive picture, including reduced lung volumes, ventilatory capacity, and gas transfer.[7] FEV1 and FVC will both be reduced, while the FEV1/FVC ratio will be normal. There is no evidence of airway reversibility after inhalation of a bronchodilator.[1]

There have been many case reports where individuals with a history of work-related exposure to bagasse were found to have typical radiographic changes to suggest bagassosis as the underlying cause of their disease. In such case reports, the chest radiograph demonstrated bilateral opacities, and computed tomography revealed patchy bilateral opacification, septal thickening, and ground-glass haziness. In many cases, bronchoalveolar lavage reveals lymphocytosis. In bronchoalveolar lavage fluid (BALF) of patients with bagassosis, hypercellularity with neutrophilia is common. Moreover, raised levels of TNF-α, IL-1β, IL-8, and IL-6 are also noted in the BALF of patients with bagassosis. or bagassosis and silicosis. Further investigation is required to assess the mechanisms underlying the different cellular and cytokine compositions in bagassosis.[15][14]

In the acute and subacute stages of the disease, high resolution computed tomography (HRCT) scan shows centrilobular nodules (central or peripheral) and ground-glass opacification.[16] However, HRCT reveals interstitial fibrosis, irregular septal thickening, glass opacification, traction bronchiectasis, and honeycombing in the chronic phase. Expiratory images may also demonstrate areas of air trapping in such patients.[17]

Lung biopsy is not usually warranted unless other commonly performed tests are inconclusive. Transbronchial biopsy has a fair diagnostic yield in acute and subacute stages of the disease. Guided by imaging, yield can be maximized by acquiring multiple samples (usually six or more) from the most affected areas of the lungs. Video-assisted thoracic surgery (VATS) or surgical open lung biopsy may provide a higher yield in chronic illness or when HRCT findings are not equivocal.[18]

Treatment / Management

Early diagnosis is critical in managing bagassosis as progression is generally preventable, and adverse effects are usually reversible. Minimizing exposure is the cornerstone of management. There is no role for drugs in the management of bagassosis; however, where elimination of antigen exposure fails at regressing the disease, corticosteroids may be warranted. Being an occupational hypersensitivity pneumonitis resulting from exposure to bagasse dust, avoiding the dust is usually all that is required to treat the condition. Reexposure to the dust is associated with the reoccurrence of the disease.[13] Symptomatic treatment with antitussives, antipyretics, fluid rehydration, rest, nutrition, and in some cases, oxygen supplementation may be required. In very severe forms of the disease, corticosteroids have shown to be beneficial.[13]

The use of low-dose macrolides has been suggested to improve inflammation; however, its benefits have not been studied in human studies.[19] The use of immunosuppression in the form of azathioprine or cyclosporine has been reported in select pediatric patients but not in the adult population.[20]

Differential Diagnosis

The differential diagnoses of the disease are numerous. They include other causes of extrinsic allergic alveolitis, such as those occurring after exposure to other organic dust (such as silicon, hay, cotton, and compost dust) and other non-allergic types of pneumonia, such as infective causes.[21][22]

Examples of hypersensitivity pneumonia that could mimic bagassosis include:

• Farmer's lung
• Suberosis
• Pigeon breeder's/bird fancier's disease
• Fungal pneumonitis[23]

Other differential diagnoses include:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Eosinophilic pneumonia
• Community-acquired pneumonia
• Miliary tuberculosis
• Silicosis
• Pulmonary edema
• Idiopathic interstitial lung disease[13][23]

Prognosis

After stopping the patient from contact with the offending bagasse dust, complete resolution of symptoms usually occurs in 1 to 6 months. The chest X-ray returns to normal in 2 to 6 months, while pulmonary function normalizes in 2 to 4 months.[1][7][13] The mortality rate of the disease is reported to be 7.5% but is likely much lower as much milder forms of the disease go undetected.[13]

Patients with evidence of lung fibrosis on lung biopsy have a poorer prognosis than those without such changes.[24]

HRCT scan can serve as a tool for predicting prognosis. A retrospective study of 69 patients revealed that the degree of fibrosis on these scans was linked with increased mortality.[25]

Morbidity and mortality related to bagassosis vary widely based on several factors, such as type, duration, and severity of the exposure. Genetic factors may also play an imperative role. The prognosis is generally less favorable once fibrotic changes occur, such as in chronic cases.[26]

Complications

Bagassosis usually resolves completely without any long-standing complications. However, similar to other pneumoconioses, several complications can arise in these patients, including interstitial lung fibrosis, chronic obstructive pulmonary disease, hemoptysis, pneumothorax, pleuritis, chronic interstitial pneumonia, and malignancy.[27] Patients may also become dependent on oxygen supplementation via long-term oxygen therapy (LTOT).