What is the treatment for hypersensitivity pneumonitis?

The treatment of hypersensitivity pneumonitis (HP) entails the avoidance of further exposure to the triggering antigen and possible pharmacological treatment with systemic corticosteroids and/or cytotoxic drugs to suppress an ongoing inflammatory or immune response.^1,2 For those with progressive fibrotic disease, antifibrotics may be an option. In those with severe HP, lung transplantation is an option.

The avoidance of exposures, if an exposure has been identified, is the most successful strategy for HP treatment. ^1,2 Survival rate is better among those with an identified inciting antigen due to the ability to avoid the antigen once it is identified. One study following 142 patients with HP from 1982-2008 reported that the rate of mortality was significantly lower among those who had an identified inciting antigen, with 39% mortality among those with an identified inciting antigen compared to 72% for those without, and a median survival of 18.2 years vs 9.3 years.³ After adjusting for factors including age, smoking history, and disease severity, survival was still longer for patients with an identified inciting antigen exposure (median of 8.75 years) than for those without (median of 4.88 years).

Reduction of exposure by using respiratory protective devices has also been shown to be a relatively effective strategy, although evidence is limited.² One 1988 study of 22 pigeon farmers with HP found that serum immunoglobulin G (IgG) levels significantly decreased in those who wore respirators (80 μg/mL at baseline, 26 μg/mL at 3 months) compared to those who did not (64 μg/mL at baseline, 105 μg/mL at 3 months).⁴

Unfortunately, in many cases of HP, the exposure factor cannot be determined.⁵ Studies have reported varying percentages of antigen-indeterminate HP. One study of 85 patients with HP found that 25% had an unknown antigen cause.⁶ Another study of patients with interstitial lung disease (ILD), 206 of which had a confirmed diagnosis of HP, found that 60% of patients had an unidentified antigen exposure.⁷ Another study of 142 patients with HP found that 53% of patients had an unidentified inciting antigen.³

If the exposure cannot be identified or remediation efforts haven’t yielded significant improvement, medications can be used. There are currently no guidelines on how to approach pharmacologic treatment for HP. Medications used in the treatment of HP include corticosteroids, immunosuppressants, and antifibrotics. Treatment strategies are personalized to individual patients depending on their presentation and disease progression.

Corticosteroids

Systemic corticosteroids can relieve acute symptoms in some patients, although their efficacy for long-term use has not been established. Due to the lack of clinical trials, there is no guideline on dose or duration.

A 1992 study (n=35) found that prednisolone increased lung function after one month of follow-up (diffusing capacity of the lung for carbon monoxide [DLCO] 18 mL/min/mm Hg with prednisolone, and 16 mL/min/mm Hg in the control group), but there was no significant difference at five years of follow-up (DLCO 23.5 mL/min/mm Hg with prednisolone, 25.6 mL/min/mm Hg control group).⁸

A 2021 retrospective study analyzed 30 patients with HP treated with prednisolone matched with 30 patients who did not; all patients were instructed to avoid exposure to causative antigens.⁹ Changes in forced vital capacity (FVC) at 6, 12, and 24 months from baseline were significantly better in the prednisolone-treated group (6.6% vs -3.2% at 6 months, 5.0% vs -4.9% at 12 months, and 0.9% vs -9.4% at 24 months). While FVC didn’t fall below baseline in the prednisolone group, it returned to roughly baseline at 2 years. Treated patients experienced lesser or no annual deterioration as assessed by the high-resolution computed tomography (HCRT) score. At 12 months, the prednisolone group had improved ground glass attenuation (median – 5 vs +1), consolidation (-1 vs +4), less traction bronchiectasis (0 vs +3), and less honeycombing (0 vs +1).

Immunosuppressants

In those with chronic HP, immunosuppressive agents can be effective in improving lung health, although this is an off-label use of these drugs. A 2017 study of 70 patients with HP followed over 11 months found that treatment with both low-dose prednisone (10-30 mg, 12.3 mg average dose at initiation, 3.75 mg average at 6 months) and mycophenolate mofetil (brand name CellCept; 1,000-3,000 mg) or azathioprine (brand names Azasan, Imuran; 100-150 mg) improved DLCO.¹⁰ After one year of treatment, DLCO increased significantly by 4.2% for the entire cohort.

Another 2017 study of 93 patients with chronic HP found that immunosuppressive therapy improved forced vital capacity (-1.2% change at 52 weeks with prednisone, -7.6% change with azathioprine, and -2.3% change with mycophenolate).¹¹

Case reports and case series have looked at other immunosuppressant medications. One 2020 case series evaluated the use of rituximab (brand name Rituximab, an anti-CD20 monoclonal antibody) in 20 patients with chronic HP whose lung function declined despite undergoing other therapy including antigen avoidance and corticosteroid therapy.¹² Although FVC continued to decline on rituximab, the rate of decline was significantly less during the six months on therapy compared to the six months prior to starting therapy (-3% [ranging from -15 to 19%] compared to -8% [ranging from -21 to 0%], p=0.0002). Larger studies are needed to validate these findings and the safety and efficacy of this therapy compared to other treatments used in HP.

Antifibrotics

Nintendanib (Ofev), an antifibrotic agent, is approved by the Food and Drug Administration (FDA) for patients with progressive fibrotic ILD, which includes patients with fibrotic HP. A double-blind, placebo controlled, phase 3 clinical trial followed 663 patients with fibrosing ILD (173 with HP) either receiving 150 mg of nintedanib twice daily or placebo for 52 weeks. The rate of decline in FVC was lesser in those who took nintedanib compared to placebo (-80.8 mL/year vs -187.8 mL/year).¹³ This effect was found in those with unusual interstitial pneumonia (UIP)-like pattern (-82.9 mL/year vs -211.1 mL/years) as well as those with other fibrotic patterns (-79.0 mL/year vs -154.2 mL/year). Additionally, the rate of mortality was lower in the nintedanib group (8.1% vs 11.5% placebo, 9.7% vs 15% for patients with UIP-like fibrotic pattern).

Lung Transplant

For those with severe HP, lung transplantation may be considered in people who are good candidates for this procedure. A retrospective cohort study of 122 patients who received a lung transplant, 31 with HP and 91 with IPF, found that survival rates were more favorable for those with HP than for those with IPF.¹⁴ At one year, HP lung transplant patients had a 96% survival rate vs 86% for IPF; at three years, it was 89% vs 67%; and at five years, it was 89% vs 49%.

References

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4. Anderson K, Walker A, Boyd G. The long-term effect of a positive pressure respirator on the specific antibody response in pigeon breeders. Clin Exp Allergy. Jan 1989;19(1):45-9. doi:10.1111/j.1365-2222.1989.tb02342.x
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9. Ejima M, Okamoto T, Suzuki T, Anzai T, Takahashi K, Miyazaki Y. Efficacy of treatment with corticosteroids for fibrotic hypersensitivity pneumonitis: a propensity score-matched cohort analysis. BMC Pulm Med. Jul 19 2021;21(1):243. doi:10.1186/s12890-021-01608-1
10. Morisset J, Johannson KA, Vittinghoff E, et al. Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis. Chest. Mar 2017;151(3):619-625. doi:10.1016/j.chest.2016.10.029
11. Adegunsoye A, Oldham JM, Fernández Pérez ER, et al. Outcomes of immunosuppressive therapy in chronic hypersensitivity pneumonitis. ERJ Open Res. Jul 2017;3(3)doi:10.1183/23120541.00016-2017
12. Ferreira M, Borie R, Crestani B, et al. Efficacy and safety of rituximab in patients with chronic hypersensitivity pneumonitis (cHP): A retrospective, multicentric, observational study. Respir Med. Oct 2020;172:106146. doi:10.1016/j.rmed.2020.106146
13. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med. Oct 31 2019;381(18):1718-1727. doi:10.1056/NEJMoa1908681
14. Kern RM, Singer JP, Koth L, et al. Lung transplantation for hypersensitivity pneumonitis. Chest. Jun 2015;147(6):1558-1565. doi:10.1378/chest.14-1543