Retrospective study of hypersensitivity reactions to chemotherapeutic agents in a thoracic oncology service.

WHAT IS KNOWN AND OBJECTIVE: With the increasing use of cancer chemotherapy agents, hypersensitivity reactions are commonly encountered. The allergic clinical symptoms are variable and unpredictable. The aim of this study was to identify the characteristics of hypersensitivity reactions and to assess the value of skin tests for platinum salts and pemetrexed in the treatment of patients with non-small cell lung cancers or malignant pleural mesothelioma. METHODS: A single-centre retrospective study was performed for 2 years. Patients treated with the drugs of interest for an advanced or metastatic non-small cell lung cancers or malignant pleural mesothelioma and who experienced hypersensitivity reactions symptoms were eligible for this study. Clinical symptoms of hypersensitivity reactions, population characteristics and administered chemotherapy regimens were identified. RESULTS: The hypersensitivity reactions frequency was rare (1.2%) and concerned 17 patients in our study. Typical clinical features of immediate hypersensitivity reactions associated with treatment were observed for nine patients (anaphylactic reactions for three cases, angioedema and hypotension associated with asthenia and heat in one case, respectively, and other cutaneous symptoms in the remaining four cases). Skin tests were positive in three patients, but only for platinum salts. The outcome after reintroduction of a negatively tested platinum salt allowed us to calculate a negative predictive value for platinum salt skin tests of 100%. For pemetrexed, skin tests were negative for all patients. WHAT IS NEW AND CONCLUSION: Skin tests could be used to diagnose hypersensitivity reactions with platinum salts or to evaluate the possibility of cross-reactions between two platinum salts. A negative skin test may predict with reasonable reliability the absence of future hypersensitivity reactions in case of reintroduction of drug infusion. Because the IgE-mediated mechanism has never been demonstrated for pemetrexed, skin tests are not valid and have no diagnostic value for this molecule. Because hypersensitivity reactions are potentially fatal adverse events, we recommend that patients who experience a hypersensitivity reactions onset should be monitored closely and clinicians must be aware of hypersensitivity reaction signs.

Cypress pollen allergy is responsible for two distinct phenotypes of allergic rhinitis different from other pollinosis.

Summary: Different phenotypes of allergic rhinitis have been identified based on the seasonality of the allergen involved. Within pollinosis, importance has to be paid to the responsible pollen species. Guidelines for clinical management are mostly based on studies performed in patients with grass pollen allergy. Only few data is available on tree pollen allergy and more specifically on cypress pollen allergy. We focused on the clinical and biological features of cypress pollen allergy to determine whether it is associated with a specific phenotype of allergic rhinitis or not. Our results suggest that cypress pollen can be responsible for two distinct phenotypes of rhinitis, both different from other pollinosis. In the most common phenotype, cypress pollen was not responsible for bronchial hyperresponsiveness or systemic inflammation. Close attention has to be paid to the allergen involved in allergic rhinitis. Different phenotypes leading to different pharmacological strategies may apply.

Aspergillus fumigatus components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis.

Aspergillus fumigatus is the causative agent of allergic broncho-pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho-pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho-pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho-pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.

Adherence in severe asthma.

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and "compliance" is usually replaced by "adherence". Assessment of adherence is addressing ethical issues, but provides important insight into difficult-to-treat asthma. Different tools have been used but none is routinely recommended. Health-related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non-adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non-adherence and all other related factors including easy-to-recognize psychological traits can help for patient's future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions.

[The obstructive sleep apnoea syndrome is not only bad for the heart!] / Le syndrome d'apnées obstructives du sommeil n'est pas mauvais que pour le cœur !

Obstructive sleep apnoea (OSA) is common in the general population, particularly in the elderly. This syndrome is frequently responsible for severe cardiovascular complications. However, the indications for its treatment in the elderly remain controversial. We report the case of a 79-year-old man with severe, undiagnosed OSA who inhaled his fixed dental bridge during sleep. The inhaled foreign body came to rest in the lumen of the left main stem bronchus. The association of obesity with a body mass index of 30kg/m2, snoring with breathing pauses reported by his partner, nocturia, morning headache and an Epworth score of 11 led to polysomnography which confirmed OSA with an apnoea/hypopnoea index of 53 per hour. This case report emphasises that OSA may constitute a risk fact for foreign body inhalation in elderly subjects due to arousal-induced hyperventilation following the apnoeic event.

[Neurofibromatosis as a cause of breathlessness]. / La neurofibromatose rend souvent essoufflé.

INTRODUCTION: Type 1 neurofibromatosis, also called "Recklinghausen's disease" is among the most frequent autosomal dominant genetic disorders, with an incidence of 1:3500 births. It mainly affects the skin and peripheral nervous system. However, in its less frequent manifestations, are tumors such as meningocele and skeletal dysplasias leading to severe clinical presentation. CASE REPORT: We report the case of a 55-year-old patient with type 1 neurofibromatosis and dyspnea due to a large left thoracic meningocele combined with a significant kyphoscoliosis, causing a severe restrictive ventilatory defect, complicated by chronic respiratory failure and pulmonary hypertension. Symptomatic treatment with non-invasive ventilation permitted an improvement of the clinical situation. CONCLUSIONS: Our observation shows the complexity of the therapeutic support of the neurofibromatosis of type 1. The contribution of non-invasive ventilation was illustrated by the arterial blood gas and clinical improvements as well as improved quality of life, with an acceptable level of inconvenience to the patient.

Air pollution and atopy.

Relationships between air pollutants and atopy can be studied within 3 different settings. In vitro, exposure of pollen to air pollutants induce morphological changes and seems to facilitate extrusion on allergenic material out of the pollen grain. In animal as well as in human experiments, air pollutants, especially diesel exhaust particulates, are able to trigger an IgE-response. Epidemiological surveys also show that air pollutants trigger symptoms in patients. In contrast, whether or not air pollutants can induce de novo allergic diseases is still a matter of debate. Some surveys suggest that, in humans also, air pollutants, especially diesel-exhaust particulates, could trigger allergic sensitization and development of atopic diseases. At home, other pollutants can be involved: volatile organic compounds have pro-inflammatory properties and favour T-cell sensitization. Relationship between exposure to secondhand tobacco smoke or occupational hazards and atopic sensitization have led to discordant results.

[Risk factors in severe asthma]. / Facteurs de risque de l'asthme grave.

Risk factors for severe acute asthma involve the patient, the environment and the society in general. In addition, there are strong interrelationships between these factors. Personal characteristics linked to acute severe asthma include age (teenagers), denial leading to poor compliance, depression with atypical symptoms in children, and some medical features of asthma associated with increased severity. Environmental factors include airborne allergens, infections, irritants such as air pollutants and passive smoking. Life events have not been extensively studied but are likely to play a predominant role. The social setting, particularly the health care system, acts as an interface between the patient and the environment. Most all asthma deaths are avoidable and related to dysfunctions in the health care system.

[Factors associated with smoking in sixth grade (11-13 years old)]. / Facteurs associés au tabagisme en classe de sixième.

Because smoking begins most often in adolescence it is important to define clearly, with a view to prevention, the motivation of an adolescent to smoke. The role of the social group is well known. The aim of this study was to evaluate the potentially preventative role of knowledge in the field of respiration and the effects of cigarette smoke on one hand and of involvement in activities involving breathing on the other. The group studied was made up of 1,802 pupils at state schools, randomly selected, in the city of Marseilles. These pupils filled in an anonymous questionnaire in the classroom. The overall percentage of non-responders was very small. Overall 10.5% if the children declared that they had already smoked, more often boys (13.1%) than girls (8.1%). In contrast to smoking by the father, smoking by the mother and siblings significantly influenced smoking in the child. The child was not influenced by smoking by a sibling of the same sex. The proportion of children having already smoked increased progressively in proportion to the number of smokers in the household. Using a logistical regression analysis the following were predictive of smoking: being a boy, having a best friend who smoked, and the number of smokers in the family. On the other hand a history of allergy, an understanding of the effects of the environment on the respiratory system, knowledge of the effects of cigarettes, and finally involvement in sport, playing a wind instrument or singing in a choir were not associated with a lower incidence of smoking. These results call into question the effectiveness of the standard preventative methods and of anti-smoking programmes that are based on such strategies.

[Thrombocytopenia induced by rifampicin not previously sensitized: a case presentation]. / Purpura thrombopénique induit par la rifampicine chez une patiente non sensibilisée : à propos d'un cas.

Thrombocytopenia induced by rifampicin in the absence of prior sensitization is exceptional, especially when it occurs in a patient without risk factors. We report the case of a patient aged 25 years with no past history of medical, surgical or knowledge of having taken rifampicin previously, who was hospitalized for treatment of thrombocytopenic purpura occurring after the initiation of fixed combination quadruple therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for pulmonary tuberculosis. The biological pretreatment and therapeutic education had not been made. The patient presented with thrombocytopenic purpura 30000/mm(3) on day 9 after the initiation of treatment. The platelet count returned to normal 10 days after discontinuation of treatment. We elected not to reintroduce rifampicin given the strong likelihood that it was responsible for this complication. We conducted a phased reintroduction of isoniazid, ethambutol and pyrazinamide. No recurrence of the thrombocytopenia occurred. Thus, the diagnosis of rifampicin-induced thrombocytopenia appears to have been confirmed and the patient tolerated the remainder of their treatment well.

[Organizing pneumonia secondary to a hiatal hernia]. / Pneumopathie organisée secondaire à une hernie hiatale.

Organizing pneumonia secondary to a hiatal hernia is a specific kind of inflammatory and fibroproliferative lung reaction due to a pulmonary aggression involving micro-inhalation of the digestive contents. The authors report the case of a 74-year-old woman presenting pneumonia of infectious speed, resistant to a triple antibiotic treatment. Clinically, her general condition changed and associated cough, fever, dirty sputum and dyspnoea. The bacteriological and immunological tests were normal. The respiratory functional explorations showed a moderate restrictive syndrome and hypoxemia. The broncho-alveolar wash found a mixed alveolite of predominantly lymphocyte and polynuclear neutrophiles. The thoracic scanner detected pleural alveolar opaqueness with the characteristic of organizing pneumonia as well as a voluminous hiatal hernia discovered by chance. No lung samples were taken because of a precarious general state of the patient and the respiratory instability. The strong corticosensitivity to the corticosteroid therapy backed up the authors' diagnostic hypothesis. The clinical and radiological evolution was good after six months of treatment. The patient benefited from a medical and then surgical treatment with a good evolution and without any recurrence.

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study.

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.