Alpha-1 antitrypsin, secreted by the liver, inhibits neutrophil elastase. Its deficiency favours the development of emphysema. Restoring a "protective" serum level in deficient patients should make ...it possible to inhibit the development of emphysema.
Human plasma-derived alpha-1 antitrypsin is a blood-derived drug sold in France under the name Alfalastin(®). The recommended posology is an I.V. administration of 60 mg/kg once a week. Human plasma-derived alpha-1 antitrypsin restores anti-elastase protection in the lower lung and prevents experimental emphysema induced by the elastasis of human neutrophils in hamster. The low number of patients with alpha-1 antitrypsin deficiency is one of the difficulties to perform sufficiently powerful randomised studies. However, randomised studies have reported the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on mortality, FEV1 decline and the frequency of exacerbations. Randomised control trials have demonstrated the efficacy of human plasma-derived alpha-1 antitrypsin perfusions on the loss of lung density assessed by CT scan.
Augmentation therapy is simple in its conception and implementation, but it is expensive. However, there are currently no other solutions.
Pulmonary alveolar proteinosis Jouneau, S; Kerjouan, M; Briens, E ...
Revue des maladies respiratoires
31, Issue:
10
Journal Article
Peer reviewed
Open access
Alveolar proteinosis (AP) is a rare disease characterized by alveolar accumulation of surfactant components, which impairs gas exchange. AP is classified into three groups: auto-immune AP defined by ...the presence of plasma autoantibodies anti-GM-CSF, the most frequent form (90% of all AP); secondary AP, mainly occurring as a consequence of haematological diseases, or following on from toxic inhalation or infections, and genetic AP, which affects almost exclusively children. AP diagnosis is suspected where chest CT-scan demonstrates interstitial lung disease with a crazy paving aspect; and confirmed by bronchoalveolar lavage, which has a milky appearance and contains periodic acid Schiff positive proteinaceous alveolar deposits. The use of surgical lung biopsy to confirm AP is less frequent nowadays. In this context, positive antibodies against GM-CSF indicates an auto-immune etiology of the AP. Concerning management, whole lung lavage is the gold standard therapy. In refractory AP, new treatments are available such as subcutaneous or inhaled GM-CSF supplementation, or rituximab infusions. The clinical course is unpredictable. Spontaneous improvement or even cure can occur, and the 5-year actuarial survival is 95%. The most frequent complications are infectious etiology.
Antisynthetase syndrome is an inflammatory myopathy frequently associated with pulmonary manifestations, especially interstitial lung diseases, and uncommonly pulmonary hypertension. In the context ...of a suggestive clinical and radiological picture, positive anti-RNA synthetase antibodies confirm the diagnosis. Anti-Jo1, anti-PL7, and anti-PL12 antibodies are the more commonly encountered. The presence of a number of extra-thoracic manifestations in association with pulmonary disease may suggest the diagnosis. These include: myalgia or muscular deficit, Raynaud's phenomenon, polyarthritis, fever, mechanics hands. Serum creatine kinase levels are usually increased. Electromyogram, muscular magnetic resonance imaging or muscle pathology are not mandatory to make the diagnosis. There is a high variability in symptoms and severity, between patients but also during the course of the disease in the same patient. The presence of an interstitial lung disease is a major prognostic factor and an indication for more intensive treatment, principally with systemic corticosteroids with or without immunosuppressive drugs. Improving respiratory physicians' knowledge of this disease, which is often revealed by its pulmonary manifestations, should help diagnosis, therapeutic management, and possibly prognosis.
Background Matrix metalloproteinases (MMPs) are likely to be relevant mediators of the extracellular matrix (ECM) degradation and airway remodelling.
Objective
We have compared the levels of MMPs, ...eotaxin and soluble interleukin 2 receptor (IL‐2R) in the plasma of healthy subjects, atopic patients and asthmatic patients.
Methods The asthmatic patients were separated into two groups, either well controlled on inhaled therapy or acute severe asthma. Patients with acute severe disease had all received systemic corticosteroids from 12 to 48 h before the blood was taken. Blood was recovered in EDTA tubes, incubated with either f MLP, PMA or vehicle for 10 min and centrifuged. MMP‐9, TIMP‐1, IL‐2R and eotaxin levels were measured in the plasma by ELISA. Moreover, the activity of MMPs was also evaluated by zymography.
Results An increased basal level of MMP‐9 and IL2‐R was observed in acute severe asthma. Following stimulation with f MLP and PMA there was an enhanced production of MMP‐9 in the plasma of all groups of patients. However, the MMP‐9 level was significantly enhanced in acute severe asthma, compared with the others. No difference was found for the TIMP‐1 level between the patients. The eotaxin level in plasma was found to be significantly lower in acute severe asthmatics compared with the others groups. Zymography technique showed a significant increased activity of MMP‐9 (92 kDa) but not MMP‐2 (66 kDa) in the plasma of patients with acute asthma.
Conclusion The increased in MMP‐9 production and activity observed in the present study suggests a process of extracellular matrix degradation in acute severe asthmatic patients and proposes MMP‐9 as a non‐invasive systemic marker of inflammation and airway remodelling in asthma.
Airway-centered interstitial fibrosis (ACIF) is a distinct type of lung interstitial fibrosis characterized by lesions centered on the airways. Several cases reported in the literature showed little ...to no effect of corticosteroids and a high mortality rate in the absence of lung transplantation. No other efficient approach is described for the treatment of this type of fibrosis. We report for the first time the case of a 44-year-old patient diagnosed with ACIF on surgical lung biopsy and stabilized with clarithromycin after failure of systemic corticosteroids. We need to confirm this benefit in other patients to ascertain the anti-inflammatory effect of macrolides, which are far less harmful compared to corticosteroids or immunosuppressant drugs.
The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail.In this retrospective multicentre study, EGPA was defined by asthma, ...eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease.The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×10
L
at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3-6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively.In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity.
Light chain deposition disease is a rare clinical entity characterized by deposition of monoclonal immunoglobulin light chains in organs. The kidneys are almost always affected, while the lung ...manifestations that have been reported, including nodular or diffuse disease, especially cystic lesions, are unusual.
We report the case of a 60-year-old man with a diffuse infiltrative lung disease characterized by numerous apical cysts. The diagnosis of light chain deposition cystic lung disease was obtained by surgical lung biopsy. Light chain deposits in the salivary glands were the only extrapulmonary manifestation. Despite 12 chemotherapy cycles, the patient's lung function and radiological appearances worsened.
This is the fourth case describing a cystic lung disease due to light chain deposition in the literature. It highlights the need for comprehensive investigations so as not to miss this rare cause of cystic lung disease, which appears to be related to a primary pulmonary lymphoproliferative disorder. The only treatment that appears to be effective is lung transplantation.
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