Response to inhaled granulocyte‐macrophage colony‐stimulating factor in patient with mild‐to‐moderate autoimmune pulmonary alveolar proteinosis—24 months of follow‐up

Abstract

IntroductionAutoimmune pulmonary alveolar proteinosis (aPAP) is a disease caused by IgG antibodies against granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Whole lung lavage (WLL) allows to remove the lipo‐proteinaceous material accumulated by the poor clearance of alveolar surfactant. However, it is a complex technique that is not exempt from complications, and in some cases, the patients are refractory, requiring the performance of several WLLs spaced apart in time.Materials and MethodsWe present the clinical, functional, and radiological evolution after 24 months of follow‐up of a patient diagnosis of aPAP refractory to WLL, with performed three therapeutic WLLs spaced 16 and 36 months and serious potentially fatal complications in the last one.Results and DisscusionAfter 24 months, no adverse effects have appeared and the great clinical, functional and radiological response is maintained. The patient has been successfully treated with inhaled recombinant human GM‐CSF sargramostim.

Whole lung lavage and GM-CSF use for pulmonary alveolar proteinosis in an infant with lysinuric protein intolerance: a case report

“…At 10 month-of-age, the patient received tracheostomy for chronic ventilation. For children with PAP with moderate to severe respiratory symptoms, the treatment of choice is WLL [ 8 , 16 , 17 ]. Therefore, WLL was first attempted under general anesthesia and mechanical ventilation using a flexible fiberoptic bronchoscope.…”

“…Nevertheless, pediatric patients are affected more often by non-autoimmune PAP, which can be of genetic origin (such as mutations of surfactant proteins), or secondary to a hematological or systemic disease (such as LPI) or toxic inhalation [ 10 ]. Based on the etiology, treatment of PAP most commonly consists of whole-lung lavage (WLL), in certain cases granulocyte-macrophage colony stimulating factor (GM-CSF) administration, and eventually lung transplantation [ 8 ]. While in autoimmune PAP there are anti GM-CSF antibodies and therefore GM-CSF administration is a promising pharmacotherapeutic approach [ 11 ]; research in LPI could not justify the role of GM-CSF administration since in LPI GM-CSF signaling pathway was found to be unaltered [ 12 ].…”

Case Report: The first reported case of pulmonary alveolar proteinosis with myasthenia gravis in a 27-year-old patient

“…aPAP is the most common presentation of PAP, and in 90% of cases it presents with GM-CSF neutralizing antibodies that produce dysfunction of the alveolar macrophage, limiting the clearance of pulmonary surfactant, causing deficiencies in gas exchange 1 .In this case, the anti GM-CSF antibodies are negative, so the diagnosis of aPAP is made by ruling out, as it cannot be related to secondary or tertiary PAP (according to the authors). Sometimes, an infectious disease can trigger a subsequent autoimmune disease.…”

“…Examples of these parameters are respiratory function tests (FVC, FFEV1, RV, DLCO, KCO), six-minute walk test (theoretical distance, HR minute 6, O2 saturation minute 6), gas exchange tests (alveolar-arterial oxygen gradient, blood gas analysis ), modification in dyspnea measured on the mMRC scale, the need for complementary oxygen therapy, etc… Radiological evolution (chest x-ray, HRCT) can also be useful (not essential, if not available comment as limitation). An example of a similar case where these concepts are addressed, which enrich the clinical case for the expert reader, has been recently presented by my research team (in case it serves as a guide) 1 .…”

“…Is it possible to ask the patient how she feels? In the case discussed by my research team 1 , after adequate treatment with inhaled GM-CSF, a patient with aPAP told us “I take a deep breath and I notice that my chest fills with air to the bottom, not like before.”…”