Screening protocols to monitor respiratory status in primary immunodeficiency disease: findings from a European survey and subclinical infection working group.

Many patients with primary immunodeficiency (PID) who have antibody deficiency develop progressive lung disease due to underlying subclinical infection and inflammation. To understand how these patients are monitored we conducted a retrospective survey based on patient records of 13 PID centres across Europe, regarding the care of 1061 adult and 178 paediatric patients with PID on immunoglobulin (Ig) G replacement. The most common diagnosis was common variable immunodeficiency in adults (75%) and hypogammaglobulinaemia in children (39%). The frequency of clinic visits varied both within and between centres: every 1-12 months for adult patients and every 3-6 months for paediatric patients. Patients diagnosed with lung diseases were more likely to receive pharmaceutical therapies and received a wider range of therapies than patients without lung disease. Variation existed between centres in the frequency with which some clinical and laboratory monitoring tests are performed, including exercise tests, laboratory testing for IgG subclass levels and specific antibodies, and lung function tests such as spirometry. Some tests were carried out more frequently in adults than in children, probably due to difficulties conducting these tests in younger children. The percentage of patients seen regularly by a chest physician, or who had microbiology tests performed following chest and sinus exacerbations, also varied widely between centres. Our survey revealed a great deal of variation across Europe in how frequently patients with PID visit the clinic and how frequently some monitoring tests are carried out. These results highlight the urgent need for consensus guidelines on how to monitor lung complications in PID patients.

[Pulmonary complications of Chronic Granulomatous Disease]. / Complications pulmonaires de la granulomatose septique chronique.

Chronic Granulomatosis Disease (CGD) is an inherited immune deficiency due to a mutation in the genes coding for the subunits of the NADPH oxidase enzyme that affects the oxidative capacity of phagocytic cells. It is characterized by increased susceptibility to bacterial and fungal infections, particularly Aspergillus, as well as complications associated with hyperinflammation and granulomatous tissue infiltration. There exist two types of frequently encountered pulmonary manifestations: (1) due to their being initially pauci-symptomatic, possibly life-threatening infectious complications are often discovered at a late stage. Though their incidence has decreased through systematic anti-bacterial and anti-fungal prophylaxis, they remain a major cause of morbidity and mortality; (2) inflammatory complications consist in persistent granulomatous mass or interstitial pneumoniae, eventually requiring immunosuppressive treatment. Pulmonary complications recurring since infancy generate parenchymal and bronchial sequelae that impact functional prognosis. Hematopoietic stem cell allograft is a curative treatment; it is arguably life-sustaining and may limit the morbidity of the disease. As a result of improved pediatric management, life expectancy has increased dramatically. That said, new challenges have appeared with regard to adults: difficulties of compliance, increased inflammatory manifestations, acquired resistance to anti-infectious therapies. These different developments underscore the importance of the transition period and the need for multidisciplinary management.

Clinical characteristics and prognostic factors of pulmonary MALT lymphoma.

Mucosa-associated lymphoid tissue-derived (MALT) lymphoma, a low grade B-cell extranodal lymphoma, is the most frequent subset of primary pulmonary lymphoma. Our objective was to evaluate the initial extent of disease and to analyse the characteristics and long-term outcome of these patients. All chest and pathological departments of teaching hospitals in Paris were contacted in order to identify patients with a histological diagnosis of primary pulmonary lymphoma of the MALT subtype. 63 cases were identified. The median age was 60 yrs. 36% of cases had no symptoms at diagnosis. 46% of patients had at least one extrapulmonary location of lymphoma. The estimated 5- and 10-yr overall survival rates were 90% and 72%, respectively. Only two of the nine observed deaths were related to lymphoma. Age and performance status were the only two adverse prognostic factors for survival. Extrapulmonary location of lymphoma was not a prognostic factor for overall survival or for progression-free survival. Treatment with cyclophosphamide or anthracycline was associated with shorter progression-free survival, when compared with chlorambucil. The survival data confirm the indolent nature of pulmonary MALT lymphoma. Better progression-free survival was observed with chlorambucil when compared with cyclophosphamide or anthracycline.

Interstitial lung disease and anti-Jo-1 antibodies: difference between acute and gradual onset.

AIM: A multicentre retrospective study was undertaken to examine patients with interstitial lung disease (ILD) with the initial clinical manifestation of an anti-synthetase syndrome (anti-Jo-1 antibodies), and to analyse the characteristics and long-term outcome of these patients according to their clinical presentation (acute or gradual onset), treatment and adverse events related to treatment. METHODS: 32 patients, 15 (47%) presenting with acute onset and associated respiratory insufficiency (group A) and 17 (53%) with gradual onset (group G) were examined. Myositis was diagnosed at admission in only 31% of cases and was observed during follow-up in 56% of cases, but the prevalence did not differ between the two groups. RESULTS: Fever and radiological patterns including diffuse patchy ground-glass opacities, basal irregular lines and consolidation on high-resolution CT scan were more frequent in group A than in group G. More patients in group G had neutrophils in the bronchoalveolar lavage fluid and autoantibodies other than anti-Jo-1 (rheumatoid factor, anti SSa/SSb) than in group A. The percentage of patients in whom the ILD improved at 3 months was significantly higher in group A than in group G (13/15 vs 9/17; p = 0.006). In contrast, after 12 months, most patients with ILD progression were in group A and were treated with corticosteroids alone. A combination of corticosteroids and an immunosuppressive drug was required in most cases (84%) at the end of the follow-up period. Severe adverse effects of treatment were observed and varicella zoster virus infection was frequent. CONCLUSIONS: Early testing for anti-synthetase antibodies, particularly anti-Jo-1, and creatine kinase determination are useful procedures in patients presenting with ILD. Treatment with corticosteroids and immunosuppressive drugs is required in most patients. At the end of the study, around two-thirds of patients had stable ILD while the other third had disease progression with respiratory insufficiency.

[Management of the pulmonary complications of haematological malignancy]. / Approche diagnostique d'une pneumopathie chez un malade atteint d'hémopathie maligne.

The high frequency of pulmonary complications of haematological malignancy and the increasing number of patients treated for these disorders make it important that the respiratory physician has a structured diagnostic approach according to: 1 the immune deficiency due to the malignancy and/or the treatment administered; 2 the factors that can modify the risk of infection (anti infection prophylaxis and/or pre-emptive treatment); 3 co-morbidities; 4 extra-pulmonary manifestations. Two main situations can be identified: The patient is aplasic: Initially the pneumonias are predominantly of bacterial origin but may be fungal if the neutropenia is prolonged. The respiratory physician is faced with two problems: 1 the diagnosis of pneumonia; this may be helped by CT scanning; 2 The choice of antibiotics; this will depend on previous investigations. The patient is not aplasic: The lung disease may have many causes, mainly infectious but also drug related, tumoral, haemorrhagic or embolic. The main problem is the correct choice of investigations to establish an aetiological diagnosis. The collection of data according to a pre-established protocol based on simple factors (study of the notes and clinical examination) is one of the key elements for improving the prognosis of these patients whose management should be multidisciplinary following a pre-defined plan.

[Lung cancer in the elderly subject]. / Cancer bronchique du sujet âgé.

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.

[The effects of inhaled steroids withdrawal in COPD]. / Impact du sevrage des corticostéroïdes inhalés dans la BPCO.

The key pathophysiological feature of chronic obstructive pulmonary disease (COPD) is an abnormal inflammatory bronchial reaction after inhalation of toxic substances. The priority is the avoidance of such toxic inhalations, but the use of anti-inflammatory drugs also seems appropriate, especially corticosteroids that are the sole anti-inflammatory drug available for this purpose in France. The risks associated with the prolonged use of these parenteral drugs are well known. Inhalation is therefore the optimal route, but inhaled drugs may also lead to adverse consequences. In COPD, there is an inhaled corticosteroids overuse, and a non-satisfactory respect of the guidelines. Consequently, their withdrawal should be considered. We reviewed seven clinical studies dealing with inhaled corticosteroids withdrawal in patients with COPD and found that included populations were heterogenous with different concomitant treatments. In non-frequent exacerbators receiving inhaled corticosteroids outside the recommendations, withdrawal appears to be safe under a well-managed bronchodilator treatment. In patients with severe COPD and frequent exacerbations, the risk of acute respiratory event is low when they receive concomitant optimal inhaled bronchodilators. However, other risks may be observed (declining lung function, quality of life) and a discussion of each case should be performed, especially in case of COPD and asthma overlap.

[Evaluation of pulmonary function in the elderly. Intergroupe Pneumo Gériatrie SPLF-SFGG]. / Evaluation de la fonction respiratoire chez le sujet âgé. Intergroupe Pneumo Gériatrie SPLF-SFGG.

Aging is associated with a progressive decrease in lung function. As a consequence of aging, individual's reserve is diminished, but this decrease is heterogeneous between individual subjects. Many factors are involved in the overall decline in lung function. The prevalence of asthma in the elderly is estimated between 6 and 10%. Mortality due to COPD is increasing, especially among older subjects. Older subjects are at an increased risk of developing chronic diseases such as Parkinson's disease, which can have consequences for lung function. Under-nutrition is also common in the elderly and can produce sarcopenia and skeletal muscle dysfunction. The presentation of respiratory disorders may differ in the elderly, especially because of a lack of perception of symptoms such as dyspnea. The impact of bronchodilatators or corticosteroids on respiratory function has not been studied in the elderly. Drugs usually used for the treatment of hypertension or arrhythmias, which are often observed with aging, can have pulmonary toxicity. There is no difference between functional evaluation in younger and older subjects but it is more difficult to find predicted values for older patients. Performing pulmonary function tests in older patients is often difficult because of a higher prevalence of cognitive impairment and/or poor coordination. When assessing pulmonary function in the elderly, the choice of tests will be depend on the circumstances, with the use of voluntary manoeuvres dependent on the condition of the patient.

[The place of inhaled corticosteroids in COPD]. / Place des corticostéroïdes inhalés dans la BPCO.

INTRODUCTION: Clinical trials have provided some evidence of a favorable effect of inhaled corticosteroids on the frequency of exacerbations and on the quality of life of patients with chronic obstructive pulmonary disease (COPD). In contrast, ICS have little or no impact on lung function decline and on mortality. STATE OF THE ART: Inhaled corticosteroids are recommended only in a minority of COPD patients, those with severe disease and repeated exacerbations and probably those with the COPD and asthma overlap syndrome. However, surveys indicate that these drugs are inappropriately prescribed in a large population of patients with COPD. Overtreatment with inhaled corticosteroids exposes these patients to an increased risk of potentially severe side-effects such as pneumonia, osteoporosis, and oropharyngeal candidiasis. Moreover, it represents a major waste of health-care spending. CONCLUSION: Primary care physicians as well as pulmonologists should be better aware of the benefits as well as the side-effects and costs of inhaled corticosteroids.

Sicca complex and infection with human immunodeficiency virus.

Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.

[Genetic susceptibility to mycobacterial disease: Mendelian disorders of the interleukin-12 -interferon-gamma axis]. / Syndrome de susceptibilite mendélienne aux infections mycobacteriennes: défauts de l'axe Interleukine-12 - Interféron-gamma.

INTRODUCTION: Environmental non tuberculous mycobacteria and Bacillus Calmette-Guerin vaccines are weakly virulent mycobacteria. Nevertheless they may cause severe diseases in otherwise healthy children with no overt immunodeficiency. Parental consanguinity and familial forms are frequently observed among these patients, therefore this syndrome was named "Mendelian Susceptibility to Mycobacterial Disease". STATE OF THE ART: In the last nine years, fife genes have been found to be mutated in patients with this syndrome: IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1. Allelic heterogeneity accounts for ten distinct genetic disorders. Clinical phenotype differs between patients. The spectrum of disease extends from early-onset overwhelming mycobacterial infection to adult-onset localized disease and tuberculosis. Impaired IFN-gamma-mediated immunity is the common mechanism of the disease, outlining its major role in mycobacterial immunity. PERSPECTIVES AND CONCLUSIONS: Better understanding of these disorders reveals an expanding clinical phenotype which justifies studying adult patients with pulmonary non tuberculous mycobacterial infection without known risk factors, severe BCGitis and recurrent tuberculosis. Molecular diagnosis makes it possible to introduce a specific regimen based on physiopathology.

Impaired T-lymphocyte-dependent immune responses to microbial antigens in patients with HIV-1-associated persistent generalized lymphadenopathy.

T-cell mediated and humoral responses directed to microbial antigens were investigated, at the time of the initial visit, in a group of 139 patients with HIV-1-related persistent generalized lymphadenopathy (PGL) enrolled in a longitudinal study. In vivo and in vitro cell-mediated responses to tuberculin were lower in patients than in controls. Differences were not significant for candidin and streptococcal antigen in vitro, whereas higher responses were observed in the patient group for cytomegalovirus antigen. Following immunization, a subgroup of patients did not have a significantly raised serum antitetanus antibody level, whereas in vitro lymphocyte proliferative responses to tetanus toxoid were lower than in controls. No association was found between these abnormalities and other immunological parameters, including the blood level of CD4+ lymphocytes. Lower responses to most microbial antigens were observed in patients with HIV-1-related symptoms in addition to lymphadenopathy, or the patients who progressed to AIDS in the 2 years following the study. Moreover, intravenous drug users showed higher responses than homosexual patients, possibly because of the influence of previous infections on immunological responses to microbial antigens.

Lymphocytic alveolitis after primary HIV infection with CMV coinfection.

Herein is a report of an adult case of primary HIV infection with cytomegalovirus coinfection causing cough, fever, and lymphocytic alveolitis. Primary HIV infection has not been previously reported as a cause of lymphocytic alveolitis.

Chlorambucil-associated pneumonitis.

A patient developed an interstitial pneumonitis while receiving chlorambucil for a chronic lymphocytic leukemia (cumulative dose, 8,340 mg). Withdrawal of drug treatment was followed by rapid improvement in the clinical condition. Bronchoalveolar lavage showed a T-lymphocytic alveolitis, whereas blood lymphocytes were predominantly of the B phenotype. The T-lymphocytic alveolitis persisted 6 weeks after drug therapy cessation with a predominant CD8+ phenotype, as observed in some hypersensitivity pneumonitis induced by drugs.

B-cell pulmonary lymphoma: gene rearrangement analysis of bronchoalveolar lymphocytes by polymerase chain reaction.

STUDY OBJECTIVES: Non-Hodgkin's lymphomas (NHLs) are clonal proliferation of B or T lymphocytes. Assessment of clonality in lymphoid proliferations uses immunochemistry and, recently, molecular biology. The aim of our study is to assess the role of immunoglobulin gene rearrangement analysis on bronchoalveolar lymphocytes to aid in the diagnosis of B-cell pulmonary NHL. PATIENTS AND METHODS: The study took place in a university hospital. There were seven consecutive patients with B-cell-type pulmonary lymphoma and nine control subjects. Gene rearrangement analysis using polymerase chain reaction (PCR) technique was performed on alveolar lymphocytes recovered by BAL. RESULTS: Analysis of the immunoglobulin heavy chain gene rearrangement showed a predominant clonal alveolar lymphocyte population in six of seven patients while all control subjects showed germline pattern. CONCLUSIONS: Gene rearrangement analysis by PCR of alveolar lymphocytes would appear to be sensitive in patients with B-cell pulmonary NHL (six of seven patients) and specific (zero of nine in the control group). This simple test should be added only in the analysis of cells recovered by BAL in patients with suspected primary and secondary B-cell pulmonary NHL.

[Giant cell myocarditis. Report of a case]. / Myocardite à cellules géantes. A propos d'un cas.

The authors report a case of giant cell myocarditis leading to rapidly progressive cardiac failure despite immuno-suppressor treatment in a 20 year old woman. The cardiac failure was successfully managed by implantation of a left ventricular assist device and then cardiac transplantation. The problems encountered underline the importance of accurate diagnosis by endomyocardial biopsy before undertaking treatment and the difficulties in the choice of appropriate method of assistance in this indication. Giant cell myocarditis is a rare cause of cardiac failure and should be considered in the differential diagnosis in view of its clinical features and risk of progression. The literature and the therapeutic implications are discussed.

[Results of abdominal x-ray computed tomography in 25 patients with the acquired immunodeficiency syndrome or the lymphadenopathy syndrome]. / Résultats de l'examen tomodensitométrique abdominal chez 25 sujets atteints de syndrome d'immuno-dépression acquise ou de syndrome lymphadénopathique.

An abdominal computed tomographic examination was performed to 20 patients with Acquired Immunodeficiency Syndrome (AIDS) and to 5 patients with Lymphadenopathy Syndrome (LAS). Intraabdominal lymph nodes were seen in 18 out of 20 cases of AIDS and in 5 cases of LAS. Lymph nodes have a normal size or are slightly enlarged but they are too numerous. Splenomegaly was found in 17 patients. Rectal modifications secondary to a proctitis were seen in the homosexual patients.