Link between statin use and interstitial lung disease

This paper was published in the Medical Journal of Australia 2007 Jan 15;186(2):91-4

Study title and authors:
Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease.

Walker T, McCaffery J, Steinfort C.
Geelong Hospital, Geelong, Victoria, Australia. timw@barwonhealth.org.au

This paper can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17223772

Dr Tim Walker from Geelong Hospital Australia describes seven patients who developed interstitial lung disease while on statin treatment. Interstitial lung disease refers to a group of lung diseases affecting the interstitium (the tissue and space around the air sacs of the lungs). (Interstitial pneumonitis is a type of interstitial lung disease).

Patient 1
(i) A 78 year old woman was admitted to hospital with shortness of breath and a dry cough.
(ii) She had been taking atorvastatin 10 mg per day for one year.
(iii) Investigations revealed extensive fibrous connective tissue (fibrosis) in the lungs.
(iv) Atorvastatin was withdrawn.
(v) Her lung function got slowly worse, and she still had shortness of breath at a three year check up.

Patient 2
(i) A 78 year old man sought medical attention at hospital after suffering from shortness of breath for three weeks.
(ii) He had been taking pravastatin 40 mg daily for ten years.
(iii) Investigations revealed extensive emphysema, fibrosis and impaired lung function.
(iv) He initially continued statin treatment and experienced respiratory failure necessitating home oxygen therapy before stopping statins.
(v) He died 18 months later of respiratory failure.

Patient 3
(i) A 74 year old woman was admitted to hospital with a cough and fever of three days duration, (consistent with pneumonia), and a background of worsening shortness of breath.
(ii) She had been taking simvastatin 10 mg daily for two years, then 20 mg daily for one year.
(iii) Investigations found extensive infiltration (fluid, fibrosis) of the lungs and a biopsy led to a diagnosis of interstitial pneumonitis.
(iv) Simvastatin was withdrawn.
(v) There was a gradual reduction in infiltrate, and her lung function was stable at a nine-month follow up.

Patient 4
(i) An 83 year old man arrived at hospital with shortness of breath which had worsened over a six month period.
(ii) He had been taking pravastatin for one year.
(iii) Investigations revealed he had fibrosis.
(iv) He stopped taking pravastatin.
(v) Despite withdrawl of pravastatin his condition slowly worsened.

Patient 5
(i) A 67 year old woman sought medical help after suffering with shortness of breath for nine months and a dry cough for six months.
(ii) She had been taking simvastatin for five years.
(iii) Investigations found patchy infiltration of her lungs and she had a TLCO of 22%. (TLCO is Transfer factor of the lung for carbon monoxide and is the extent to which oxygen passes from the air sacs of the lungs into the blood. A low TLCO indicates fibrosis and restrictive lung disease).
(iv) She stopped taking simvastatin.
(v) She had a marked improvement: TLCO increased to 51% after one month, and improved further to 65% after one year.

Patient 6
(i) A 68 year old man was admitted to hospital with worsening shortness of breath and hypoxia. (Hypoxia is where there is not enough oxygen getting to the tissues of the body).
(ii) He had been taking simvastatin for two years.
(iii) Investigations revealed he had inflammation and fibrosis in the lungs.
(iv) He continued to take simvastatin.
(v) He died nine months later from heart disease exacerbated by interstitial lung disease.

Patient 7
(i) A 64 year old man sought medical attention for worsening shortness of breath and a dry cough.
(ii) He had been taking atorvastatin 20 mg daily for three years, then 40 mg daily for two years.
(iii) Investigations found the patient had fibrosis. he had a TLCO of 44%.
(iv) Atorvastatin was withdrawn.
(v) He had an improvement in his condition. His TLCO increased to 52% after two months.

Dr Walker also reviewed some other adverse side effects that statins may cause.

He found:
(a) The most commonly reported adverse effects include gastrointestinal upset, headache, rash and a dose-dependent elevation in levels of liver transaminases (enzymes).
(b) The most potentially serious, adverse effects include myopathy (muscle disease) and polyneuropathy (life threatening neurological disorder that occurs when many nerves throughout the body malfunction simultaneously).
(c) Statins have been associated with lung diseases, lupus-like syndromes and muscle and skin inflammation diseases.
(d) Many patients take statin therapy for many months or years before these symptoms develop.
(e) Their clinical features vary in severity from mild dry cough and rash through to severe and progressive respiratory failure.

Dr Walker concluded: "We hope that our description of our patients and review of the possible role of statins in interstitial lung disease will raise awareness of the potential association between statin therapy and this uncommon and often fatal condition".