Reversibility of refractory bronchiolitis caused by aspiration a

Reversibility of refractory bronchiolitis caused by aspiration associated with achalasia (03-09-2009)


Khaled Mansour1, Ger H. Koek2,4, Robert Jan van Suylen3,4, Marjolein Drent1,4. Dept of Respiratory Medicine1, Dept of Internal medicine, division of Gastroenterology/Hepatology2, Dept of Pathology3, ild care centre4, Maastricht University Medical Centre, The Netherlands, the Netherlands.



Reflux may cause oxidative stress, lung inflammation and finally irreversible lung fibrosis. Gastroesophageal reflux (GER) may be associated with several airway manifestations such as chronic bronchitis, recurrent pneumonia, chronic cough , hoarseness, and asthma. is a fatal lung disease with unknown etiology [1]. Moreover, patients with idiopathic pulmonary fibrosis (IPF) have shown high incidence of GER either in symptomatic or asymptomatic form [2,3]. Efficient treatment of GER with appropriate doses of acid suppressant agents is therefore an important part of treatment of patients with IPF[4].


Case history

A 59-years old woman was referred to our hospital because of refractory idiopathic interstitial pneumonia. At presentation her main symptoms were progressive dyspnoea, exercise intolerance and cough and repeated episodes of upper airway infections. She was known with achalasia, a mammacarcinoma and a nefrectomy right because of a Grawitz tumour. She was treated with methotrexate and folic acid for the rheumatoid arthritis. This was stopped 2 month before referral as a drug-induced pneumonitis was considered. However, after stopping methotrexate her clinical condition did not improved. She was known almost 30 years with achalasia of distal esophagus and she has undergone several times esophageal dilatation without much improvement. She still suffered from weight gain due to dysphagia, regurgitation and chronic aspiration especially during de night.
Physical examination revealed fine crepitations at auscultation. She had a moderate hypoxemia (pO2 8.7kPa, breathing room air), high serum C-reactive protein (254 mg/l), a white blood cell count of 16.3 109/l and a normal number of eosinophils.
The diffusing capacity and vital capacity were decreased.



Figure 1  Chest x-ray of 59 year old woman with achalasia.



The chest radiograph (figure 1) demonstrated a diffuse interstitial pattern with basal predominant ground-glass abnormalities, which was confirmed by the a high resolution CT (HRCT) scan showing a geographic (mosaic) distribution of ground- glass (figure 2).





Figure 2  HRCT scan of the thorax of 59 year old woman with GER-induced bronchiolitis:
before the operation (A, B, C; March 2004) after correction of the esophageal stricture (D, E, F; March 2005).


A bronchoscopy showed no endobronchial abnormalities. Bronchoalveolar lavage (BAL) fluid cell analysis revealed a slightly increase of the lymphocytes (17.6%), of the polymorphonuclear neutrophils (PMNs; 5.4%), and of the eosinophils (Eos; 10.4%). Moreover, foamy macrophages were seen (figure 3). Cultures were negative.


Figure 3. ‘Foamy alveolar macrophage’.  
Figure 4. Non-necrotizing granulomatous
bronchiolitis with numerous giant cells.

An open lung biopsy showed mainly peri-bronchiolar inflammatory infiltrates composed of lymphocytes, plasma cells and histiocytes with many giant cells compatible with aspiration bronchiolitis (figure 4). A severe stasis of food and fluid was found related to the persisted achalasia. Chronic reflux was considered to be related to the interstitial damage.
Initially, this patient was treated with repeated esophageal dilatation without obvious success. Therefore, a laparoscopic cardiomyotomy according to Heller and an anterior fundoplication (Dor) was performed in 2004.

Figure 5  Pre- and post-operatively of lower esophageal stricture.


Thereafter, no food or liquid stasis has been observed. Moreover, after 3 months the lung damage was nearly resolved and the lung function tests became within normal limits (figure 6). Till now, the pulmonary problems did not returned.


Figure 6  Before and after distal oesophagus myotomy (Heller Dor method).


The presented case developed an ‘aspiration-induced pneumonitis’ as a result of achalasia and chronic aspiration. Surgical intervention appeared to be obviously efficient. Pulmonary manifestations of GER are not uncommon and many studies have shown a possible causal relation between GER and various upper and lower airway manifestations including asthma and IPF [3,4]. Fibroblast foci are indicative of IPF and appear to be a cellular attempt to repair the damaged alveolus. Although this progressive, often fatal, clinical syndrome is thought to be dependent on alveolar injury of unknown origin, significant clinical and preclinical evidence points to gastric acid as a causative harmful agent [5]. Graded instillation of various forms of acid in several animal models resulted in aspiration-induced lung injury, including pulmonary fibrosis in pigs. Moreover, compelling clinical data suggest that a high percentage of patients with idiopathic pulmonary fibrosis also experience abnormal esophageal acid exposure, without necessarily experiencing the typical symptoms of gastroesophageal reflux disease (GERD) [2-4]. The exact etiology of GERD associated pulmonary manifestations remains unknown. A direct contact of aspirated gastric acid with airway mucosa or vagovagal reflex through gastric aspiration-induced irritation of distal portion of the esophagus might be associated [6].
Considering the high mortality rates associated with idiopathic pulmonary fibrosis, evolving clinical knowledge concerning underlying causation with regard to gastric acid is crucial [2-4].



In certain unexplained cases of idiopathic pneumonitis ‘reflux associated aspiration bronchiolitis’ should be considered instead of ‘idiopathic’ interstitial damage and, more important, appropriate anti-reflux treatment together with antioxidants may lead to substantial clinical improvement and reversibility.



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  2. Raghu G, Weycker D, Edelsberg J, et al. Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006; 174: 810-16.
  3. Raghu G. The role of gastroesophageal reflux in idiopathic pulmonary fibrosis. Am J Med 2003 Aug 18;115 Suppl 3A:60S-64S.
  4. Raghu G, et al. High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis. Eur Repir J 2006: 27: 136–42.
  5. Gharaee-Kermani M, Hu B, Thannickal VJ, et al. Current and emerging drugs for idiopathic pulmonary fibrosis. Expert Opin Emerg Drugs 2007;12: 627-46.
  6. Fass R, Achem SR, Harding S, et al. Review article: supra-oesophageal manifestations of gastro-oesophageal reflux disease and the role of night-time gastro-oesophageal reflux. Aliment Pharmacol Ther 2004;20; Suppl 9:26-38.


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