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Correspondence |

Corticosteroids May Worsen Gastroesophageal Reflux in Patients With Idiopathic Pulmonary FibrosisResponse FREE TO VIEW

Filippo Luca Fimognari, MD; Ruggero Pastorelli, MD
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Affiliations: Unit of Respiratory Diseases, Division of Internal Medicine, ASL Roma G-Leopoldo Parodi-Delfino Hospital, Colleferro, Rome, Italy,  University of Washington Medical Center, Seattle, WA

Correspondence to: Filippo Luca Fimognari, MD, Via F. Verdinois 6/11A6–00159, Rome, Italy; e-mail: filippo.fimognari@virgilio.it



Chest. 2007;132(5):1719-1720. doi:10.1378/chest.06-2659
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Published online

Gastroesophageal reflux (GER) is highly prevalent in patients with idiopathic pulmonary fibrosis (IPF).1We read with interest the study by Raghu et al2 (March 2006) about four patients with IPF complicated by GER. All patients had refused therapy with corticosteroids or immunomodulatory agents and were treated only with antireflux drugs. GER was diagnosed using 24-h esophageal pH monitoring; if needed, drug doses were increased to obtain adequate suppression of acid GER, as verified by repeating pH study. Interestingly, clinical improvements were temporally associated with introduction or adjustment of the antireflux therapy, while deteriorations tended to follow treatment discontinuation. After a mean 4-year period since diagnosis, all patients were alive and stable. The authors speculate that the microaspiration of acid droplets in the lungs may favor inflammation with ensuing fibrosis, and that this vicious circle can be interrupted by the antireflux therapy.

IPF is usually treated with oral corticosteroids. According to a systematic review,3 however, there is no evidence for their efficacy. Moreover, corticosteroids cause serious complications that should be weighed against the potential benefits, particularly in older and frail patients.

Importantly, oral prednisone directly worsened reflux in asthma.4As this side effect is supposed to occur also in IPF patients, it would seem reasonable to suspend corticosteroids once GER is instrumentally ascertained. Many clinicians, however, prefer to add proton-pump inhibitors to corticosteroids without investigating the possible underlying GER. In addition, GER may be the only cause of chronic cough,5 but this condition is often attributed to IPF deterioration and, therefore, erroneously treated with enhanced doses of corticosteroids. In conclusion, the role of corticosteroids in IPF should be revisited also in view of the potential negative impact of GER on the progression of this disease.

The authors have no conflicts of interest to disclose.

The author has no conflict of interest to disclose.

Raghu, G, Freudenberger, TD, Yang, S, et al (2006) High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.Eur Respir J27,136-142. [PubMed] [CrossRef]
 
Raghu, G, Yang, S, Spada, C, et al Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest2006;129,794-800. [PubMed]
 
Richeldi, L, Davies, HR, Ferrara, G, et al Corticosteroids for idiopathic pulmonary fibrosis.Cochrane Database Syst Rev2003;(3),CD002880. [PubMed]
 
Lazenby, JP, Guzzo, MR, Harding, SM, et al Oral corticosteroids increases esophageal acid contact times in patients with asthma.Chest2002;121,625-634. [PubMed]
 
Brown, KK Chronic cough due to chronic interstitial pulmonary diseases: ACCP evidence-based clinical practice guidelines.Chest2006;129,180S-185S. [PubMed]
 
To the Editor:

Indeed, it is well known to clinicians that patients treated with oral corticosteroids, regardless of the indication, manifest new and/or worsened symptoms suggestive of abnormal gastroesophageal reflux (GER). Thus, several patients receiving corticosteroids take over-the-counter remedies for such symptoms while taking corticosteroids, and several clinicians prescribe medications to suppress symptoms of GER for patients receiving corticosteroids.

In the context of management of idiopathic pulmonary fibrosis (IPF), the longstanding and ongoing practice of using corticosteroids has evolved into a standard of care without evidence supported by well-designed, prospective clinical trials that compare the efficacy and safety of a treatment regimen with true-placebo control subjects. Thus, the comments and concerns raised by Fimognari and Pastorelli to our article1are appropriate. Since it is unknown if any treatment regimen (including corticosteroids) that is being currently used for patients with IPF is effective when compared to no specific treatment, and since there is no evidence to support lone-corticosteroid treatment for IPF, it is hoped that the lingering standard of care using corticosteroids alone as a treatment will fade away soon while evidence that will determine an efficacious treatment regimen for IPF is being pursued.2

Given the inevitable poor prognosis associated with the diagnosis of IPF and a safe and efficacious treatment regimen is yet to be determined, it is most appropriate to decrease and/or avoid further risks and minimize comorbid conditions for patients confronted with this fatal disease. Although the results of a recent clinical trial favors the use of combined prednisone with azathioprine and N-acetylcysteine (NAC) compared to prednisone plus azathioprine (the Idiopathic Pulmonary Fibrosis International Group Exploring N-Acetylcysteine I Annual [IFIGENIA] study conducted in Europe published by Demedts et al3) and an earlier clinical trial4 suggested the potential benefits of combined prednisone plus azathioprine compared to prednisone alone, it is unknown if such regimens that include prednisone as a treatment agent improves the outcome of patients in IPF when compared to control subjects receiving absolutely no treatment at all (the “true-placebo” controls subjects).

Despite the caution raised in interpreting results of clinical trials in IPF and plea that I have made to refrain the use of treatment regimen without firm evidence,2,5the concern raised by Fimognari and Pastorelli is appreciated since the current international consensus statement on the management guidelines for IPF6 and the evidence provided by the IFIGENIA study will tempt clinicians to continue to try corticosteroids with or without combinations with agents such as azathioprine and NAC. Thus, the potential for enhanced risk for comorbid conditions and for possible progression of IPF if the hypothesis of abnormal GER contributing to IPF holds. While it is hoped that ongoing and future clinical trials will provide the needed evidence to recommend a specific treatment regimen for IPF, the Hippocratic oath and longstanding philosophy of “do no harm” must be respected in managing such medical problems.

References
Raghu, G, Yang, S, Spada, C, et al Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest2006;129,794-800. [PubMed] [CrossRef]
 
Raghu, G Idiopathic fibrosis treatment: options in pursuit of evidence-based approaches.Eur Respir J2006;28,463-465. [PubMed]
 
Demedts, M, Behr, J, Buhl, R, et al High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med2005;353,2229-2242. [PubMed]
 
Raghu, G, Depaso, WJ, Cain, K, et al Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.Am Rev Respir Dis1991;144,291-296. [PubMed]
 
Johnson, WC, Raghu, G Clinical trials in idiopathic pulmonary fibrosis: a word of caution concerning choice of outcome measures.Eur Respir J2005;26,755-758. [PubMed]
 
Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.Am J Respir Crit Care Med2000;161,646-664. [PubMed]
 

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Tables

References

Raghu, G, Freudenberger, TD, Yang, S, et al (2006) High prevalence of abnormal acid gastro-oesophageal reflux in idiopathic pulmonary fibrosis.Eur Respir J27,136-142. [PubMed] [CrossRef]
 
Raghu, G, Yang, S, Spada, C, et al Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest2006;129,794-800. [PubMed]
 
Richeldi, L, Davies, HR, Ferrara, G, et al Corticosteroids for idiopathic pulmonary fibrosis.Cochrane Database Syst Rev2003;(3),CD002880. [PubMed]
 
Lazenby, JP, Guzzo, MR, Harding, SM, et al Oral corticosteroids increases esophageal acid contact times in patients with asthma.Chest2002;121,625-634. [PubMed]
 
Brown, KK Chronic cough due to chronic interstitial pulmonary diseases: ACCP evidence-based clinical practice guidelines.Chest2006;129,180S-185S. [PubMed]
 
Raghu, G, Yang, S, Spada, C, et al Sole treatment of acid gastroesophageal reflux in idiopathic pulmonary fibrosis: a case series.Chest2006;129,794-800. [PubMed] [CrossRef]
 
Raghu, G Idiopathic fibrosis treatment: options in pursuit of evidence-based approaches.Eur Respir J2006;28,463-465. [PubMed]
 
Demedts, M, Behr, J, Buhl, R, et al High-dose acetylcysteine in idiopathic pulmonary fibrosis.N Engl J Med2005;353,2229-2242. [PubMed]
 
Raghu, G, Depaso, WJ, Cain, K, et al Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial.Am Rev Respir Dis1991;144,291-296. [PubMed]
 
Johnson, WC, Raghu, G Clinical trials in idiopathic pulmonary fibrosis: a word of caution concerning choice of outcome measures.Eur Respir J2005;26,755-758. [PubMed]
 
Idiopathic pulmonary fibrosis: diagnosis and treatment: international consensus statement.Am J Respir Crit Care Med2000;161,646-664. [PubMed]
 
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