Macrolides: A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia?

doi:10.1378/chest.128.5.3611

Chest

Volume 128, Issue 5, November 2005, Pages 3611-3617

https://doi.org/10.1378/chest.128.5.3611 Get rights and content

Some macrolides have been found to exert anti-inflammatory effects. Lung diseases such as asthma, panbronchiolitis, cystic fibrosis, and bronchiectasis are thought to respond to the immunomodulatory properties of macrolides. We report three cases of idiopathic bronchiolitis obliterans organizing pneumonia, now called cryptogenic organizing pneumonia, and three cases of radiation-related bronchiolitis obliterans organizing pneumonia that responded to macrolide therapy. An explanation of why macrolides may have anti-inflammatory effects in patients with these syndromes is discussed. These cases help to reinforce accumulating data that macrolides are beneficial as anti-inflammatory agents and organizing pneumonia may be another pulmonary disease that can benefit from such therapy.

Section snippets

CASE 1

A 72-year-old man with a history of prostate cancer was well until 3 weeks prior, when cough productive of green sputum developed accompanied by low-grade fever. A chest radiograph showed a right lower lobe infiltrate, and CT of the chest revealed multiple bilateral patchy infiltrates predominately in the lower lobes as well as subcentimeter pulmonary nodules (Fig 1,top). The latter were present for two years and were presumed metastatic from the prostate. Because the nodules were stable, he

CASE 2

A 76-year-old man with colon cancer was referred to the pulmonary service for abnormal chest radiograph findings. The patient was status post right hemicolectomy and was receiving chemotherapy for a local recurrence that was complicated by profuse diarrhea and vomiting requiring hospitalization. Two weeks after hospital discharge, although the diarrhea and vomiting had subsided, cough, pleuritic pain, and dyspnea with exertion developed but no fever or chills. There was no history of aspiration

CASE 3

A 65-year-old woman was well until 3 months prior, when she began to experience malaise with nausea, vomiting, and weight loss. She underwent a CT scan of the chest, abdomen, and pelvis that was remarkable for bilateral lower lobe consolidations with air bronchograms, as well as bilateral nodules in the upper lobes. She was placed on clarithromycin and was referred for further evaluation. At the initial visit, the patient had lost 20 lb despite resolution of the vomiting. She denied cough,

CASES 4, 5, AND6

These cases are thought to represent radiation-related BOOP.3, 4, 5 These patients had tissue that either confirmed the diagnosis and/or ruled out other diagnoses such as infection or malignancy.

DISCUSSION

Organizing pneumonia is a common nonspecific histologic pattern seen in a wide variety of settings, including infection, granulomatous disease, vasculitis, hemorrhage, eosinophilic pneumonia, drug-induced lung injury, and many others. Pathologically, it is characterized by intraluminal polypoid plugs of granulation tissue extending continuously from the distal air spaces into alveolar ducts and alveoli. Other features include chronic inflammation of the walls of surrounding alveoli, increased

CONCLUSION

There are accumulating data that reinforce the hypothesis of a direct immunosuppressive effect of macrolides on neutrophil and T-cell functions. Phagocytes and their cytokines, oxidants, and proteolytic enzymes are important effectors in some inflammatory diseases such as asthma, CF, bronchiectasis, and DPB. It is in these pulmonary disorders that macrolides have been shown to have some therapeutic efficacy, not as anti-infectious agents but as anti-inflammatory drugs. We believe our cases add

ACKNOWLEDGMENTS

The authors thank Dr. Maureen Zakowski for interpretation of the pathology slides and Yvonne Herd for preparation of the manuscript.

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Organizing Pneumonia
2021, Encyclopedia of Respiratory Medicine, Second Edition
Organizing pneumonia is characterized by a histologic pattern of plugs of granulation tissue within alveoli, alveolar ducts, and bronchioles. This nonspecific finding, in the setting of characteristic clinical and radiographic features, defines cryptogenic organizing pneumonia when no etiology is found or secondary organizing pneumonia if a cause or exposure is identified. Prognosis is usually good with the majority of patients responding rapidly to corticosteroids, though relapses are not uncommon.
Everolimus induced organizing pneumonia in a patient with tuberous sclerosis complex
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Organizing pneumonia is characterized by a distinct histologic pattern in the lung interstitium and presents clinically as hypoxemia, fever, cough, and dyspnea that is not attributable to concurrent infection. Typical etiologies of this condition include inflammatory disease, malignancy, toxic inhalation, and an array of medications including the mTOR inhibitor everolimus. In this report, we describe the case of a female with tuberous sclerosis complex on everolimus therapy for renal angiomyolipomas who presented to the hospital with persistent cough, dyspnea, and fevers and bilateral lower lobe opacities on chest X-ray despite multiple courses of antibiotic therapy. Bronchoscopy was performed with transbronchial biopsies, and results demonstrated a lymphocytic predominance and pathologic findings of intraluminal plugs composed of fibroblasts and myofibroblasts consistent with organizing pneumonia. Everolimus therapy was discontinued and patient completed a steroid course with resolution of symptoms. To our knowledge, this is the first published case of organizing pneumonia secondary to everolimus in a patient with tuberous sclerosis complex.
Stereotactic body radiotherapy for lung cancer patients with idiopathic interstitial pneumonias
2017, Radiotherapy and Oncology
To compare toxicity and survival after stereotactic body radiotherapy (SBRT) between lung cancer patients with or without idiopathic interstitial pneumonias (IIPs), and to investigate the potential value of SBRT for the patients.
Among lung cancer patients receiving SBRT between 2005 and 2016, we evaluated those treated with a total dose of 40–60 Gy in five fractions with curative intent who either were staged as cT1-4N0M0 or experienced postoperative isolated local recurrence. We analyzed the incidence of radiation pneumonitis (RP) in all patients and local recurrence and overall survival (OS) in T1a-2a patients.
A total of 508 patients were eligible, including 42 with IIPs. The median follow-up was 32.3 (6.0–120.9) months. Significantly more patients with IIPs had grade ≥3 RP than did those without IIPs (12% vs. 3%, p = 0.009). The 2-year local recurrence rate was low in both groups (3.4% vs. 5.6%, p = 0.38). The 2-year OS rate was significantly lower in the patients with IIPs (42.2% vs. 80.9%, p < 0.001), although death from lung cancer was comparable (p = 0.74).
SBRT achieved excellent local control with acceptable pulmonary toxicity in lung cancer patients with IIPs. SBRT can be a reasonable option for early lung cancer patients with IIPs.
Early Onset Noninfectious Pulmonary Syndromes after Hematopoietic Cell Transplantation
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Factors associated with the relapse of cryptogenic and secondary organizing pneumonia
2017, Respiratory Investigation
Citation Excerpt :
In patients with OP and BAL neutrophilia (a threshold of 10% neutrophils), Hotta found significant increases in neutrophil chemotactic activity (NCA) and IL-8 level, which is a major mediator of neutrophil chemotaxis [7], and showed that the administration of erythromycin significantly reduced NCA, IL-8 level, and the number of neutrophils in the BALF while being effective against OP. Other reports have also described the effectiveness of macrolides in patients with COP, as these prevent the activation of neutrophils and Th1 cells [16,17]. These findings may explain our result that BAL neutrophilia correlated with OP relapse.
Organizing pneumonia (OP) is a histopathological response pattern to lung inflammation. It is clinically classified into cryptogenic OP and secondary OP, which is associated with various clinical conditions. Rapid resolution with corticosteroids and frequent relapses are common in OP. However, few studies have investigated the factors associated with OP relapse.
The medical records of 75 patients with biopsy-proven OP, diagnosed between January 2010 and August 2015, who underwent corticosteroid therapy were retrospectively reviewed. Initially, the patients were all treated successfully; however, 31 patients experienced relapse thereafter (R group), whereas the others did not (NR group; 44 patients). The clinical, radiological, and pathological characteristics and administered corticosteroid doses were compared between the two groups.
The neutrophil percentage in the bronchoalveolar lavage (BAL) fluid and the level of fibrin deposition in lung biopsy specimens were higher in the R group than in the NR group (P=0.01 and P=0.002, respectively). The multivariate analysis demonstrated that both factors were statistically significant predictors of OP relapse.
A high neutrophil percentage in the BAL and the level of fibrin deposition in lung biopsy specimens are considered predictive factors of OP relapse during the tapering or after the cessation of steroid therapy. Patients without these findings may be treated with low-dose corticosteroids.
Extracorporeal CO<inf>2</inf> removal as life support system for a severe organizing pneumonia
2016, Revue de Pneumologie Clinique
Les agressions pulmonaires aiguës sont régulièrement rencontrées dans les services de réanimation. Le dommage alvéolaire diffus (DAD) en est l’atteinte histologique la plus grave. La pneumonie organisée (PO), dont le traitement de référence est la corticothérapie, peut mimer un DAD. La réponse au traitement pouvant être différée, pour limiter les effets délétères de la ventilation mécanique prolongée, les méthodes d’assistance respiratoire extracorporelle peuvent être utilisées. Nous présentons une observation d’épuration extracorporelle du CO₂ (ECCO₂R) en attente de l’efficacité d’une corticothérapie administrée pour une PO sévère.
Dans un contexte grippal, l’absence de résolution de l’atteinte respiratoire est rapportée à une PO. Une ECCO₂R est utilisée en attente d’amélioration de la fonction pulmonaire sous corticothérapie tout en permettant de mettre en œuvre une ventilation « ultra protectrice ». Cette stratégie a permis de lever les sédations autorisant le réveil de la patiente et la réhabilitation plus précoce que ne l’aurait permis une stratégie conventionnelle requérant une adaptation au ventilateur.
Cette observation souligne les difficultés diagnostiques et thérapeutiques des atteintes pulmonaires en réanimation. La PO est une entité qui doit être reconnue. L’ECCO₂R peut être proposée pour les cas les plus sévères en attente de l’efficacité des corticoïdes.
Acute lung injuries are usually found in intensive care unit. The diffuse alveolar damage (DAD) is the associated histological pattern and the most severe end-stage of the disease. Organizing pneumonia (OP), for which corticosteroids are the reference therapy, can mimic DAD. While postponing the response to treatment, to limit mechanical ventilation side effects, extracorporeal membrane oxygene can be proposed. We present a case of a severe OP for which extracorporeal CO₂ removal (ECCO₂R) is used as a bridge to recovery under corticosteroid therapy.
In the context of a flu-like syndrome, the non-recovery of a lung impairment is reported to a severe OP. ECCO₂R is applied when using an ultraprotective ventilation and while waiting for lung healing under corticosteroid. This strategy allowed successful recovery, early physical therapy and active mobilization.
This observation presents the diagnostic and therapeutic difficulties of the lung parenchymental disease in intensive care. OP must be recognized. ECCO₂R can be used in severe OP as a bridge to recovery while waiting for the corticosteroid efficacy.

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Opinions and HypothesesMacrolides: A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia?

Section snippets

CASE 1

CASE 2

CASE 3

CASES 4, 5, AND6

DISCUSSION

CONCLUSION

ACKNOWLEDGMENTS

Mayo Clin Proc

J Allergy

J Allergy Clin Immunol

Chest

Chest

Chest

Chest

Chest

ATS/ERS international multidisciplinary consensus classification of idiopathic interstitial pneumonia: general principles and recommendations.

Am J Respir Crit Care Med

Bronchiolitis obliterans organizing pneumonia.

N Engl J Med

Migratory organizing pneumonitis “primed” by radiation therapy.

Eur Respir J

A newly recognized syndrome - radiation-related bronchiolitis obliterans organizing pneumonia.

Respiration

Bronchiolitis obliterans organizing pneumonia in cancer: a case series.

Respir Med

Anti-inflammatory effects of roxithromycin in patients with aspirin-intolerant asthma.

Clin Exp Allergy

Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients.

Am Rev Respir Dis

Opinions and Hypotheses
Macrolides: A Treatment Alternative for Bronchiolitis Obliterans Organizing Pneumonia?