Introduction
A broad-spectrum antibacterial agent is Nitrofurantoin. Women frequently use Nitrofurantoin to treat acute and recurrent urinary tract infections (UTIs), and it is a powerful chemotherapy agent for those who experience repeated UTIs. Women make up 85 percent of patients who have Nitrofurantoin-associated pulmonary responses when they first arrive. This finding could be explained by the fact that women are more likely to get recurring UTIs than men. Just over one percent of patients receiving Nitrofurantoin have reported experiencing pulmonary reactions. Even less often occurs acute and severe pulmonary toxicity. In one trial, only three out of 16101 initial Nitrofurantoin doses resulted in acute pulmonary toxicity that necessitated hospitalization. In general, patients who appear acutely are younger, with a median age of 59 years, than those who present chronically, having a median age of 68 years.
What Are the Clinical Manifestations of Nitrofurantoin-Associated Pulmonary Toxicity?
The literature has identified some clinical signs and symptoms of Nitrofurantoin pulmonary toxicity, including:
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Acute Presentation: The majority (83 percent) of clinical presentations are acute. Indicative constitutional signs like fever, a maculopapular rash (skin lesion), arthralgia (joint pain), and exhaustion characterize the acute reaction. Dry cough, chest discomfort, and dyspnea (shortness of breath) are typical pulmonary signs and symptoms. Eosinophilia at the periphery is frequent. Eosinophilia (high eosinophil count) is frequently absent at first, although it can develop after a few days of treatment or with subsequent occurrences. Nitrofurantoin-related pulmonary responses do not seem to be dose-related. Eight percent of acute reactions appear within the first eight to nine days, and all acute reactions on Nitrofurantoin medication happen within a month. Following repeated therapy, acute reactions may return in a considerably shorter amount of time (within 24 hours). Fluconazole combined with chronic Nitrofurantoin has been known to cause acute lung toxicity. Patients who have previously been exposed to Nitrofurantoin without experiencing any pulmonary effects have been reported to develop acute pulmonary toxicity.
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Subacute Presentation: The majority of documented instances of subacute presentation had Nitrofurantoin treatment for at least one month and up to six months before symptoms started to appear. Dry cough, dyspnea, low-grade fever, and cyanosis (bluish discoloration of the skin) are typical symptoms. IgG levels, antinuclear antibody (ANA) titers, and erythrocyte sedimentation rate may all be high in laboratory results.
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Chronic Presentation: Patients on Nitrofurantoin therapy for six months to six years may develop chronic presentation and lung fibrosis. Dry cough and increasing dyspnea that worsens over weeks to years are the typical presenting symptoms.
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It has also been reported that fulminant pulmonary bleeding can cause hemoptysis and respiratory failure.
What Is the Pathogenesis Of Nitrofurantoin-Associated Pulmonary Toxicity?
It is unknown how Nitrofurantoin causes lung toxicity. Based on clinical, experimental, and animal research, the following pathways have been proposed:
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Direct oxidant-mediated damage to lung parenchymal cells.
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The effects of hyperoxia speed up the damage caused by Nitrofurantoin.
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Alveolar epithelial damage was caused by lymphocytes activated by Nitrofurantoin.
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Lung endothelial cell damage.
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Immune system-mediated responses.
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Hypersensitive responses.
How Is Nitrofurantoin-Associated Pulmonary Toxicity Diagnosed?
1. Pathological Findings:
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Acute Nitrofurantoin pulmonary toxicity manifests pathologically as focal bleeding, vasculitis (blood vessel inflammation), alveolitis (inflammation of alveoli), fibrinous alveolar exudates, reactive type II pneumocytes, and mild interstitial inflammation.
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Diffuse interstitial fibrosis (a collection of illnesses that gradually scar lung tissue), vascular sclerosis (abnormal hardening of blood vessels), fibrosis and thickening of the alveolar septa, interstitial inflammation, and bronchiolitis obliterans (chronic lung disease) with organized pneumonia are typical pathologic findings in chronic Nitrofurantoin pulmonary toxicity.
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Rare reports of Nitrofurantoin lung damage have included desquamative interstitial pneumonia (chronic lung inflammation), hypersensitivity pneumonitis (immune system disorder affecting the lungs), and giant cell interstitial pneumonia (lung disease).
2. Radiographic Findings:
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On chest radiographs, parenchymal alterations brought on by Nitrofurantoin pulmonary toxicity are virtually always bilateral and mostly confined in the lower lung zones. Although parenchymal alterations in unilateral pleural effusions are possible, they are uncommon.
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A high-resolution computed tomography (CT) scan of the chest could reveal subpleural irregular linear opacities, patchy consolidation, and ground glass opacities. In chronic Nitrofurantoin poisoning, reticular pattern and traction bronchiectasis are also frequently observed. Although a widespread reticular pattern and concomitant lung parenchyma distortion typically indicate a developed and permanent fibrosis, recovery of these abnormalities has been seen in six weeks to one year after the drug has been stopped.
3. Pulmonary Function Tests:
Reduced forced vital capacity (FVC), single-breath carbon monoxide diffusion capacity (DLCO), and total lung capacity (TLC) are the typical results of pulmonary function testing. Normal lung volumes may be seen even though DLCO is always lowered.
4. Radionuclide Scanning:
Radionuclide scanning reveals inflammation of the lung parenchyma due to Nitrofurantoin-induced pulmonary damage. The very sensitive test for the identification of pulmonary inflammation is gallium-67 citrate lung scintigraphy. Early Nitrofurantoin lung toxicity detection has been done using gallium scans. In cases of acute Nitrofurantoin lung toxicity, ventilation-perfusion lung imaging may also reveal a momentary reverse ventilation-perfusion mismatch. After quitting the medicine for 24 to 48 hours, these alterations typically return to normal.
5. Combination of Lung and Liver Toxicity:
Patients with chronic hepatitis or excessively high hepatic transaminases may also exhibit signs of chronic lung Nitrofurantoin toxicity. Antinuclear and anti-smooth muscle antibodies are present in these patients with chronic hepatitis.
How Is Nitrofurantoin-Associated Pulmonary Toxicity Treated?
Acute pulmonary response patients experience a symptomatic recovery after ceasing their Nitrofurantoin therapy in approximately 47 percent of cases after one day, 88 percent of cases after three days, and nearly all cases after two weeks. Patients with subacute or persistent reactions may need two to three months to recover. Around 60 percent of these patients may continue to have pulmonary fibrotic alterations. Although the function of corticosteroids has not been thoroughly studied, a corticosteroid trial may be beneficial for patients with hypoxemia or respiratory symptoms.
Conclusion
A bactericidal antibiotic, Nitrofurantoin, affects a number of the bacterial cell's metabolic pathways. It is used daily as a preventative measure for recurring urinary tract infections as well as first-line empiric therapy for uncomplicated cystitis. As a result, women make up the majority of patients who have a Nitrofurantoin-related adverse event. The termination of Nitrofurantoin therapy forms the basis of treatment. Although acute reactions are more frequent, it is crucial to watch out for persistent symptoms.
