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Syndrome of Iron Pill Aspiration* FREE TO VIEW

Pyng Lee, MD; Daniel A. Culver, DO; Carol Farver, MD; Atul C. Mehta, MBBS, FCCP
Author and Funding Information

*From the Departments of Pulmonary and Critical Care Medicine (Drs. Lee, Culver, and Mehta) and Histopathology (Dr. Farver), Cleveland Clinic Foundation, Cleveland, OH.

Correspondence to: Atul C. Mehta, MBBS, FCCP, Department of Pulmonary and Critical Care Medicine/A90, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland OH 44195; e-mail: mehtaa1@ccf.org



Chest. 2002;121(4):1355-1357. doi:10.1378/chest.121.4.1355
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Published online

Bronchial stenosis (BS) consequent to iron pill aspiration (IPA) has been observed in few reported cases. This condition is often irreversible and may necessitate lobectomy in severe cases. Unlike most foreign bodies (FBs), the iron pill disintegrates in the airway and cannot be detected on bronchoscopy. However, bronchial biopsy and lung tissue may reveal iron deposits along with airway inflammation months after the aspiration. Thus, IPA can be diagnosed by a triad of aspiration, airway inflammation, and iron deposits on histology even in the absence of an FB. We report a case of IPA with BS in which the diagnosis was established by bronchial biopsy and was successfully managed with balloon bronchoplasty and therapy with topical mitomycin C.

Figures in this Article

Tracheobronchial stenosis, as a result of granulomatous diseases14 and mechanical causes such as prolonged endotracheal intubation or cuffed tube tracheostomy,5has been well-documented in the literature. However, bronchial stenosis (BS) as a consequence of foreign body (FB) aspiration, and especially the aspiration of medicinal pills, is rare.6 We report a case of iron pill aspiration (IPA) with BS in which the diagnosis was established, in the absence of an FB, by bronchial biopsy of the stenosed airway. This was managed successfully with balloon bronchoplasty (BB) and therapy with topical mitomycin C (MC).

A 69-year-old woman with hypothyroidism, hypertension, and previous multiple strokes, and who had undergone a partial gastrectomy, had been receiving daily doses of ferrous sulfate. She remembered aspirating an iron pill in October 1999 when she experienced choking, wheezing, and cough. The findings of a chest radiograph were normal. Two months later, she was hospitalized with pneumonia and required assisted ventilation. A bronchoscopy at that time revealed extensive inflammation of the truncus and left lower lobe bronchus (LLLB). No FB was detected, but the truncus was lined with a greenish brown necrotic material (Fig 1 ).

As she remained symptomatic, a repeat bronchoscopy 3 months later revealed near-total obstruction of the truncus and LLLB with purulent secretions from the left lower lobe. The respiratory cultures were negative for mycobacteria and fungi but were positive for methicillin-resistant Staphylococcus aureus. The patient was treated with IV vancomycin, and a BB was attempted without success. She was referred to our institution for further management.

The truncus and LLLB were found to be 90% and 70% stenosed, respectively, the etiology of which was unclear at that time. Near-total patency was established by BB, and endobronchial injection of methylprednisolone was carried out. The patient began receiving therapy with oral steroids and antibiotics after the procedure.

Despite treatment, she developed recurrent pneumonia from restenosis of the affected bronchi. Endobronchial biopsies of the truncus 1 year after the episode of aspiration revealed ferric iron in the subepithelial connective tissue with foci of granulation tissue and fibrosis (Fig 2 ), which confirmed the patient’s history of IPA. She underwent another BB, which was followed by a topical application of MC with informed consent. With the aid of flexible bronchoscopy, a single dose of 1 mL MC at 0.2 mg/mL was applied over the wall of each affected bronchus for 5 min (Fig 3 ).

On review 6 weeks after the procedure, the following results of ventilatory function tests were normal: FVC, 3.02 L (101% of predicted); and FEV1, 3.02 L (92% of predicted). Good patency of the truncus and the LLLB was demonstrated on bronchoscopy.

The aspiration of an FB is a serious and potentially fatal problem. Over the past 25 years, the mean number of deaths from FB inhalation is 3,238 per year, making it the sixth leading cause of accidental death in the United States.7In adults, the majority of episodes of FB aspiration occur in the sixth or seventh decade of life due to the failure of airway protective mechanisms.8

The diagnosis of FB aspiration continues to pose a challenge to clinicians as medical history and physical signs are often nonspecific and chest radiographs can be normal in one fourth of the cases. However, a symptom triad of cough, wheezing, and decreased air entry should alert the doctor to suspect FB aspiration.

Most FBs remain intact in the bronchial tree for a long time,9although granulation tissue causing airway obstruction, atelectasis, and bronchiectasis can occur. Late sequelae of inhaled FBs such as BS and bronchiectasis can be avoided if an early bronchoscopy is performed. This is especially important for organic FB and drugs such as nortriptyline and iron pills in which the free iron eluted from the pill causes inflammation and fibrosis of the bronchial wall.1011

The iron pill was not detected on bronchoscopy 2 months after the aspiration in our patient, but the biopsy specimens obtained a year later stained positive for iron and the patient continued to experience airway inflammation and fibrosis. As she was not a candidate for surgical bronchoplasty, a repeat BB was performed.

To date, reports of IPA have been rare, but BS as a late occurrence has been consistently described.12,10 In two reports,12 BS was established at diagnosis and the specimens showed an FB granulomatous reaction with fibrosis, and in a third report, Godden et al11 reported a spectrum of manifestations ranging from acute mucosal damage to scarring and granulation tissue. It is therefore not surprising that BS may be a late sequelae of IPA.

Topical MC, an antitumor antibiotic isolated from Streptomyces caespitosus, has been used notably in patients with glaucoma and after pterygium surgery.1213 The high success rate of topical MC is attributable to its inhibitory effect on fibroblast proliferation while allowing for epithelial regrowth.14This beneficial effect was further demonstrated in five pediatric patients with recurrent tracheal cicatrix after tracheal reconstruction surgery.15

Topical MC at a relatively low concentration of 0.2 mg/mL was chosen because of its established efficacy and safety in ophthalmic surgery1617 as well as its demonstrable success in preventing laryngotracheal stenosis following airway injury in dogs.18 Thus, it was used with analogous intent in our patient to prevent recurrent BS, and this novel method showed good results at 6 weeks.

Our case lends support to reports in the literature that show that IPA causes significant airway inflammation and BS due to iron deposition in the bronchial wall. As the pill disintegrates in the airway, it is usually not detected on bronchoscopy. Thus, a high degree of suspicion is necessary to make the diagnosis. We propose that a triad of symptoms (ie, aspiration, intense airway inflammation with BS, and iron particles in bronchial biopsy specimens) constitutes the syndrome of IPA, even in the absence of an FB. We would also recommend that the use of iron pills should be avoided in patients with swallowing disorders. However, if BS develops from IPA, it can be managed with BB. The role of MC remains to be studied.

Abbreviations: BB = balloon bronchoplasty; BS = bronchial stenosis; FB = foreign body; IPA = iron pill aspiration; LLL = lower lower lobe; LLLB = left lower lobe bronchus; MC = mitomycin C

Figure Jump LinkFigure 1. Bronchoscopy shows extensive inflammation of the truncus, which was lined with greenish brown necrotic material.Grahic Jump Location
Figure Jump LinkFigure 2. Bronchial wall with ciliated respiratory epithelium and underlying submucosal brown deposits of ferric iron is shown. Chronic inflammation and some fibrosis are present adjacent to the iron. A Prussian blue stain for iron confirmed the finding (hematoxylin-eosin, original ×200).Grahic Jump Location
Figure Jump LinkFigure 3. The method of topical mitomycin application following bronchoplasty is shown.Grahic Jump Location
Tarkka, M, Anttila, S, Sutinen, S (1988) Bronchial stenosis after aspiration of an iron tablet.Chest93,439-441. [PubMed] [CrossRef]
 
Mizuki, M, Onizuki, O, Aoki, T, et al A case of remarkable bronchial stenosis due to aspiration of delayed release iron tablet.Nihon Kyobu Shikkan Gakkai Zasshi1989;27,234-239. [PubMed]
 
Daum, TE, Specks, U, Colby, TV, et al Tracheobronchial involvement in Wegener’s granulomatosis.Am J Respir Crit Care Med1995;151,522-526. [PubMed]
 
Chung, HS, Lee, JH Bronchoscopic assessment of the evolution of endobronchial tuberculosis.Chest2000;117,385-392. [PubMed]
 
Andrews, MJ, Pearson, FG Incidence and pathogenesis of tracheal stricture following cuffed tube tracheostomy with assisted ventilation.Ann Surg1971;173,249-263. [PubMed]
 
Baharloo, F, Veyckemans, F, Francis, C, et al Tracheobronchial foreign bodies: presentation and management in children and adults.Chest1999;115,1357-1362. [PubMed]
 
National Safety Council.. Injury facts (formerly Accident Facts).1999,9-12 National Safety Council. Itasca, IL:
 
Limper, AH, Prakash, UB Tracheobronchial foreign bodies in adults.Ann Intern Med1990;112,604-609. [PubMed]
 
Cunanan, OS The flexible fiberoptic bronchoscope in foreign body removal: experience in 300 cases.Chest1978;73,725-726. [PubMed]
 
Johnson, DR, Yew, D Aspiration of nortriptyline.Am J Emerg Med1994;12,337-338. [PubMed]
 
Godden, DJ, Kerr, KM, Watt, SJ, et al Iron lung: bronchoscopic and pathological consequences of aspiration of ferrous sulphate.Thorax1991;46,142-143. [PubMed]
 
Lee, DA Antifibrosis agents in glaucoma surgery.Invest Ophthalmol1994;35,3789-3791
 
Rubinfeld, RS, Stein, RM Topical mitomycin C for pterygia: is single application appropriate?Ophthalmic Surg Lasers1997;28,662-669. [PubMed]
 
Khaw, PT, Doyle, JW, Sherwood, MB Prolonged localized tissue effects from 5 minute exposures to fluorouracil and mitomycin-C.Arch Ophthalmol1993;111,263-267. [PubMed]
 
Ward, RF, April, MM Mitomycin-C in the treatment of tracheal cicatrix after tracheal reconstruction.Int J Pediatr Otorhinolaryngol1998;44,221-226. [PubMed]
 
Frutcht-Pery, J, Siganos, CS, Ilsar, M Intraoperative application of topical mitomycin C for pterygium surgery.Opthalmology1996;103,674-677
 
Sugar, A Who should receive mitomycin C after pterygium surgery?Ophthalmology1992;99,1645-1646. [PubMed]
 
Eliashar, R, Eliashar, I, Esclamado, R, et al Can topical mitomycin prevent laryngotracheal stenosis?Laryngoscope1999;109,1594-1600. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Bronchoscopy shows extensive inflammation of the truncus, which was lined with greenish brown necrotic material.Grahic Jump Location
Figure Jump LinkFigure 2. Bronchial wall with ciliated respiratory epithelium and underlying submucosal brown deposits of ferric iron is shown. Chronic inflammation and some fibrosis are present adjacent to the iron. A Prussian blue stain for iron confirmed the finding (hematoxylin-eosin, original ×200).Grahic Jump Location
Figure Jump LinkFigure 3. The method of topical mitomycin application following bronchoplasty is shown.Grahic Jump Location

Tables

References

Tarkka, M, Anttila, S, Sutinen, S (1988) Bronchial stenosis after aspiration of an iron tablet.Chest93,439-441. [PubMed] [CrossRef]
 
Mizuki, M, Onizuki, O, Aoki, T, et al A case of remarkable bronchial stenosis due to aspiration of delayed release iron tablet.Nihon Kyobu Shikkan Gakkai Zasshi1989;27,234-239. [PubMed]
 
Daum, TE, Specks, U, Colby, TV, et al Tracheobronchial involvement in Wegener’s granulomatosis.Am J Respir Crit Care Med1995;151,522-526. [PubMed]
 
Chung, HS, Lee, JH Bronchoscopic assessment of the evolution of endobronchial tuberculosis.Chest2000;117,385-392. [PubMed]
 
Andrews, MJ, Pearson, FG Incidence and pathogenesis of tracheal stricture following cuffed tube tracheostomy with assisted ventilation.Ann Surg1971;173,249-263. [PubMed]
 
Baharloo, F, Veyckemans, F, Francis, C, et al Tracheobronchial foreign bodies: presentation and management in children and adults.Chest1999;115,1357-1362. [PubMed]
 
National Safety Council.. Injury facts (formerly Accident Facts).1999,9-12 National Safety Council. Itasca, IL:
 
Limper, AH, Prakash, UB Tracheobronchial foreign bodies in adults.Ann Intern Med1990;112,604-609. [PubMed]
 
Cunanan, OS The flexible fiberoptic bronchoscope in foreign body removal: experience in 300 cases.Chest1978;73,725-726. [PubMed]
 
Johnson, DR, Yew, D Aspiration of nortriptyline.Am J Emerg Med1994;12,337-338. [PubMed]
 
Godden, DJ, Kerr, KM, Watt, SJ, et al Iron lung: bronchoscopic and pathological consequences of aspiration of ferrous sulphate.Thorax1991;46,142-143. [PubMed]
 
Lee, DA Antifibrosis agents in glaucoma surgery.Invest Ophthalmol1994;35,3789-3791
 
Rubinfeld, RS, Stein, RM Topical mitomycin C for pterygia: is single application appropriate?Ophthalmic Surg Lasers1997;28,662-669. [PubMed]
 
Khaw, PT, Doyle, JW, Sherwood, MB Prolonged localized tissue effects from 5 minute exposures to fluorouracil and mitomycin-C.Arch Ophthalmol1993;111,263-267. [PubMed]
 
Ward, RF, April, MM Mitomycin-C in the treatment of tracheal cicatrix after tracheal reconstruction.Int J Pediatr Otorhinolaryngol1998;44,221-226. [PubMed]
 
Frutcht-Pery, J, Siganos, CS, Ilsar, M Intraoperative application of topical mitomycin C for pterygium surgery.Opthalmology1996;103,674-677
 
Sugar, A Who should receive mitomycin C after pterygium surgery?Ophthalmology1992;99,1645-1646. [PubMed]
 
Eliashar, R, Eliashar, I, Esclamado, R, et al Can topical mitomycin prevent laryngotracheal stenosis?Laryngoscope1999;109,1594-1600. [PubMed]
 
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