Jessica Cemlyn-Jones

Nanoparticles, nanotechnology and pulmonary nanotoxicology

The recently emergent field of Nanotechnology involves the production and use of structures at the nanoscale. Research at atomic, molecular or macromolecular levels, has led to new materials, systems and structures on a scale consisting of particles less than 100 nm and showing unique and unusual physical, chemical and biological properties, which has enabled new applications in diverse fields, creating a multimillion-dollar high-tech industry. Nanotechnologies have a wide variety of uses from nanomedicine, consumer goods, electronics, communications and computing to environmental applications, efficient energy sources, agriculture, water purification, textiles, and aerospace industry, among many others. The different characteristics of nanoparticles such as size, shape, surface charge, chemical properties, solubility and degree of agglomeration will determine their effects on biological systems and human health, and the likelihood of respiratory hazards. There are a number of new studies about the potential occupational and environmental effects of nanoparticles and general precautionary measures are now fully justified. Adverse respiratory effects include multifocal granulomas, peribronchial inflammation, progressive interstitial fibrosis, chronic inflammatory responses, collagen deposition and oxidative stress. The authors present an overview of the most important studies about respiratory nanotoxicology and the effects of nanoparticles and engineered nanomaterials on the respiratory system.

Sensitization to profilin in the Central region of Portugal.

BACKGROUND Profilin is a panallergen found in pollens and fruits. Sensitization to this protein may explain some sensitization to multiple pollen species. We aimed to evaluate sensitization to profilin in patients suffering from respiratory allergy sensitized to pollens, in the Central region of Portugal. METHODS Patients were evaluated for asthma symptoms, rhinitis, conjunctivitis and food allergy. Skin prick tests (SPT) to aeroallergens including 12 different pollens and profilin (nPho d 2) were performed. The patients were divided into two study groups according to the region of residence: A--inland region and B--coastal region. RESULTS A total of 370 patients were evaluated (277-group A; 93-group B). 65.9% showed positive skin prick tests and 76.2% were positive to pollens (87.1%-group A; 42.85%-group B; p<0.0001). All the patients sensitized to pollens had rhinitis (p=0.001). Sensitization to profilin was associated with pollen sensitization (p=0.014). 43 patients were sensitized to profilin (40-group A; 3-group B; p=0.006). 21.0% of patients sensitized to pollens, were also sensitized to profilin. 39 patients were sensitized to at least two pollens (p<0.0001). Four profilin and pollen sensitized patients had oral allergy syndrome complaints to melon. This syndrome was related with profilin sensitization (p=0.001). CONCLUSIONS It is advisable to perform SPT to profilin, particularly in the Inland region, for a better differential diagnosis between cross-reactivity and true sensitization to pollens. The results together with the medical history may support the choice for a specific immunotherapy option.

Evaluation of bone mineral density in cystic fibrosis patients

Patients with cystic fibrosis (CF) have an increasing life span and osteoporosis has become a more recognised problem in these patients. The pathogenesis of low bone mineral density (BMD) in CF seems to be multifactorial and the aim of this study was to assess the prevalence of low BMD in a group of CF outpatients and to relate the findings with the variables studied. The study included 22 patients aged between 14 and 45 years (mean age 26.3). Two of the subjects were lung transplant patients. BMD was assessed by dual-energy X-ray absorptiometry (DEXA) at the lumbar spine (LS) and femoral neck (FN). This data was correlated with serum 25-hydroxy vitamin D (25-OHD) levels, BMI and the forced expiratory volume in one second (FEV1). BMD (Z-score and T-score) ranged from 0.6 to -6 and from 0.5 to -6.7 at LS; at FN the scores ranged from 0.6 to -3.9 and from 0.6 to -4.1. The mean serum 25-OHD concentration (12,57 ng/ml) was at the low end of the normal range (10-60 ng/ml). On average patients did not present with malnutrition, however BMI ranged from 15.2 to 33.7 kg/m2. Lung function status was assessed by FEV1; 64% of patients had FEV1 below 80% and within this group four patients had a FEV1 under 40%. There was a positive correlation between low BMD and 25-OHD concentrations and also between BMD and FEV1. There was no linear correlation between BMD and BMI.

Proteinuria in cystic fibrosis: a possible correlation between genotype and renal phenotype

OBJECTIVE To assess proteinuria in patients with cystic fibrosis (CF), and to correlate proteinuria with genotype, CF-related diabetes and disease severity. METHODS A prospective study was carried out over a six-month period and involving 22 CF patients. After the collection and analysis of 24-h urine samples, the patients were divided into two subgroups: protein excretion < 150 mg/day (low-proteinuria); and protein excretion > 150 mg/day (highproteinuria). Patient charts were reviewed to obtain data on genotype and CF-related diabetes. Disease severity was assessed based on acute exacerbations in the last six months and FEV1 measured during the study period. To assess the correlation between genotype and proteinuria, the two main mutations (DeltaF508 and R334W) were evaluated. Due to the existence of genotype DeltaF508/R334W, two categories were created to enable statistical analysis, DeltaF508 being evaluated in category 1 and R334W being evaluated in category 2. RESULTS The DeltaF508 mutation tended to be associated with normal protein excretion: 100% of the low-proteinuria subgroup patients were considered DeltaF508 in category 1, compared with 86.7% in category 2. Protein excretion tended to be higher in patients with the R334W mutation: 60.0% of the high-proteinuria subgroup patients were considered R334W in category 1, compared with 80.0% in category 2 (p = 0.009 and p = 0.014, respectively). No significant association was found for any of the other variables. CONCLUSIONS The results suggest that genotype is associated with renal phenotype, depending on the mechanism by which the genotype alters the function of the cystic fibrosis transmembrane conductance regulator gene.

Sarcoidosis: A less common presentation

The clinical presentation of sarcoidosis is diverse and in over 90% of patients there is pulmonary involvement. The most common features of the radiographic findings at the time of diagnosis are bilateral hilar lymphadenopathy and pulmonary infiltration. The authors report the case of a young female patient who presented with multiple bilateral nodular shadows on chest radiograph. Surgical biopsy revealed non-necrotizing granulomas with occasional multinucleated giant cells compatible with sarcoidosis. Although this was a case of stage III pulmonary disease, the patient was asymptomatic, lung function tests were normal and there were no signs of extrathoracic involvement. Spontaneous remission occurred without treatment as shown on high resolution CT scan follow-up, one year later.

Avaliação da densidade mineral óssea em doentes com fibrose quística

Patients with cystic fibrosis (CF) have an increasing life span and osteoporosis has become a more recognised problem in these patients. The pathogenesis of low bone mineral density (BMD) in CF seems to be multifactorial and the aim of this study was to assess the prevalence of low BMD in a group of CF outpatients and to relate the findings with the variables studied. The study included 22 patients aged between 14 and 45 years (mean age 26.3). Two of the subjects were lung transplant patients. BMD was assessed by dualenergy X-ray absorptiometry (DEXA) at the lumbar spine (LS) and femoral neck (FN). This data was correlated with serum 25-hydroxy vitamin D (25-OHD) levels, BMI and the forced expiratory volume in one second (FEV1). BMD (Z-score and T-score) ranged from 0.6 to -6 and from 0.5 to -6.7 at LS; at FN the scores ranged from 0.6 to -3.9 and from 0.6 to -4.1. The mean serum 25-OHD concentration (12,57 ng/ml) was at the low end of the normal range (10-60 ng/ml). On average patients did not present with malnutrition, however BMI ranged from 15.2 to 33.7 kg/m2. Lung function status was assessed by FEV1; 64% of patients had FEV1 below 80% and within this group four patients had a FEV1 under 40%. There was a positive correlation between low BMD and 25-OHD concentrations and also between BMD and FEV1. There was no linear correlation between BMD and BMI. Rev Port Pneumol 2008; XIV (5): 625-634

Poland syndrome and pneumothorax: the compelling evidence of an association

Poland Syndrome is a rare congenital deformity which mainly occurs sporadically but occasional familial cases have been reported. It is characterized by unilateral absence of pectoralis muscle, typically in association with other deformities of the ipsilateral chest wall and/or upper limbs. According to recent classifications, the pectoralis muscle anomaly alone is enough to establish diagnosis. It predominantly affects the right hemithorax (67-75%), with rare bilateral cases described. The most commonly accepted causal mechanism is related to disruption of blood supply through the subclavian artery during embryogenesis. Incidence varies from 1/70000 to 1/100000 live births, with a male to female ratio of 2-3 to 1. Due to mild or even nonexistent functional impairment, the condition is thought to be under-reported and underdiagnosed. Surgical correction is recommended in cases of significant functional or aesthetic impairment. We report the case of a 19 year-old male, admitted to the emergency room presenting with left-sided chest pain 24 hours after onset. He had no other complaints and there was no precipitating event, such as, trauma or infection.The patient was a non-smoker; with no relevant personal or family past medical history. Physical examination showed the patient to be tachycardic and slightly polypneic. Thoracic inspection showed hypoplasia of the left thoracic wall due to the underdevelopment of the left pectoralis muscle and decreased chest expansion. No other structural abnormalities were observed on the affected side of the torso. Also on the left hemithorax, there was hyperresonance to percussion and absent breath sounds on ausculation. Chest x-ray showed a large left lung pneumothorax; a chest tube was successfully placed with clinical improvement and total lung expansion. Thoracic computer tomography (Figures 1 and 2) revealed hypoplasia of the major pectoralis muscle confirming the diagnosis of Poland Syndrome and ruled out other abnormalities. There was full resolution of the pneumothorax and the chest tube was removed after four days.

Diffuse alveolar hemorrhage - review of an interstitial lung disease clinic

Background: Diffuse alveolar haemorrhage (DAH), is a life-threatening condition, arising from pulmonary microvasculature, with a nonspecific clinical and radiologic presentation. In 33% of cases there is no haemoptysis and there are diffuse alveolar infiltrates, usually requiring confirmation by bronchoalveolar lavage (BAL). Prompt treatment is crucial and underlying etiology, generally systemic autoimmune and coagulation disorders, must be managed. Differential diagnosis is extensive. Objectives and Methods: Retrospective review of the Interstitial Lung Disease Clinic between 2013 and 2017 assessing patients with a diagnosis of DAH for demographic, clinical, radiologic, laboratorial and histologic data. Results: There were 6 patients (2 males and 4 females). Three had prior medical history of autoimmune disorders under immunosuppression: 1 systemic lupus erythematosus; 1 granulomatosis with polyangiitis; 1 microscopic polyangiitis, the last two had kidney biopsy. One patient had iatrogenic hypocoagulation from warfarin medication; another had malignant hypertension, with hypertensive nephroangiosclerosis and one presented with severe blood dyscrasia, due to myelodysplastic syndrome. Only 2 patients had haemoptysis, all had anaemia, 4 requiring blood transfusions and 2 aminergic support. All had diffuse bilateral cotton-like densities and positive haemorrhagic BAL, two with hemosiderin deposits. One patient died on admission, the remaining five continue in follow-up under targeted treatment. Conclusion: DAH is a severe disorder, with nonspecific presentation, caused by a wide spectrum of disease, as demonstrated by this series. Diagnosis requires high clinical suspicion and a thorough work-up.