Spontaneous pneumothorax-When do we need to intervene?

BACKGROUND: Pneumothorax can be classified as traumatic, iatrogenic or spontaneous (SP), which can be subdivided into primary spontaneous pneumothorax (PSP), a condition without preexisting lung disease, or secondary spontaneous pneumothorax (SSP) a complication of a preexisting lung disease. Recurrence rate of PSP is 30% whereas for SSP rate is unknown. This article explores the experience of a tertiary center over 20 years. METHODS: A retrospective case review of patients hospitalized with pneumothorax to investigate the natural history and treatment of SP in a young population in a single tertiary center was conducted. A search of the digital archive (going back to 01/01/1995) of Sheba Medical Center identified hospitalized patients below the age of 40. RESULTS: The database was composed of the records of 750 patients (612 males, 138 females) who were hospitalized. The recurrence risk for SP after nonoperative treatment was significantly higher. Women were found to have an increased risk of SSP when having SP (OR 2.78). Asthma was the most prevalent disease causing SSP in young people. CONCLUSIONS: In this large cohort, we found that operative procedure has clear protective effect from recurrence in SP, so surgery should be positively considered when treating SP in hospitalized patients. Among young people and particularly in pediatric patients, when females have a SP, we strongly recommend looking for primary lung disease. More studies are needed to determine the risk factors and produce clear guidelines regarding surgery as first treatment.

Advanced Lung Disease in Patients with Cystic Fibrosis Is Associated with Low Diffusion capacity.

BACKGROUND: The single-breath diffusing capacity of the lungs (DLCOSB) test measures the extent to which carbon monoxide (CO) passes from the lung air sacs into the blood. The accessible alveolar volume (VASB) is measured by inert gas during a 10-second period. The single-breath transfer coefficient of the lung for carbon monoxide (KCOSB) is the DLCOSB divided by VASB. Cystic fibrosis (CF) disease comprises progressive airway obstruction with bronchiectasis and parenchyma fibrosis. Yet, the KCOSB appears insignificant in the assessment of pulmonary function in CF. OBJECTIVES: To challenge the precision of normal KCOSB in CF. METHODS: The authors collected pulmonary function tests (PFT) data from 74 confirmed CF patients (mean age 26 ± 10 years) with various levels of pulmonary disease severity. Tests included spirometry, DLCOBP, and body plethysmography (BP). Anatomical dead space was calculated by deducting anatomical dead space from total lung capacity TLC(BP) to establish alveolar volume (VABP) and to determine KCOBP. We also included individual data of arterial pCO2 blood-gas level. RESULTS: KCOSB values were normal or higher in most patients, regardless of patient FEV1 value (R2 = 0.2204; P < 0.02). In contrast, the measurements of KCOBP were low corresponding with low FEV1 values, and negatively correlated with the elevation of trapped air and pCO2 levels (R2 = 0.1383; P = 0.0133, P > 0.05, respectively). CONCLUSIONS: The 10- second perfusion time of the inert gas during DLCOSB represent the communicative alveolar volume in CF patients with advanced pulmonary disease. The findings justify the use of DLCOSB with the deterioration of FEV1 and elevation of pCO2 levels.

The Value of Measuring Inspiratory Capacity in Subjects With Cystic Fibrosis.

BACKGROUND: Inspiratory capacity (IC) is often overlooked as an important measured index of spirometry in patients with cystic fibrosis (CF). Abnormally low IC may indicate the onset of static/dynamic hyperinflation, which may be accompanied by dyspnea and an increase in the work of breathing. This cross-sectional study sought to determine whether measuring IC during spirometry, may add clinical value to FEV1 measurements in CF subjects. METHODS: Anthropometric, clinical, spirometry, and static lung volume data were gathered retrospectively from 98 of 165 subjects with CF (mean ± SD age 26.8 ± 11.0 y) registered in The Edmond and Lily Safra Children's Hospital, Sheba Medical Centre, Israel. We compared the IC (% predicted) to FEV1, static lung volumes, and hospitalization days/year. RESULTS: IC decreased alongside FEV1 decline but at a slower pace (r2 = 0.32). Incremental trapped air, as measured by residual volume (RV), and a rapid elevation in the ratio of RV to total lung capacity occurred when IC deteriorated below 60% predicted values. The unique combination of IC < 50% predicted and FEV1 > 40% predicted induced an increase of up to 125 hospitalization days/year compared to subjects having IC > 50% predicted (up to 73 d/y, P < .001). CONCLUSIONS: Measuring IC in CF subjects may reveal silent worsening of lung function as indicated by a decline in IC < 50% predicted while FEV1 is still > 40% predicted. This condition may lead to inefficient breathing at high lung volumes, which may explain a subjective sensation of breathlessness and lead to an increase in hospitalization days/year.

Respiratory care in familial dysautonomia: Systematic review and expert consensus recommendations.

BACKGROUND: Familial dysautonomia (Riley-Day syndrome, hereditary sensory autonomic neuropathy type-III) is a rare genetic disease caused by impaired development of sensory and afferent autonomic nerves. As a consequence, patients develop neurogenic dysphagia with frequent aspiration, chronic lung disease, and chemoreflex failure leading to severe sleep disordered breathing. The purpose of these guidelines is to provide recommendations for the diagnosis and treatment of respiratory disorders in familial dysautonomia. METHODS: We performed a systematic review to summarize the evidence related to our questions. When evidence was not sufficient, we used data from the New York University Familial Dysautonomia Patient Registry, a database containing ongoing prospective comprehensive clinical data from 670 cases. The evidence was summarized and discussed by a multidisciplinary panel of experts. Evidence-based and expert recommendations were then formulated, written, and graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. RESULTS: Recommendations were formulated for or against specific diagnostic tests and clinical interventions. Diagnostic tests reviewed included radiological evaluation, dysphagia evaluation, gastroesophageal evaluation, bronchoscopy and bronchoalveolar lavage, pulmonary function tests, laryngoscopy and polysomnography. Clinical interventions and therapies reviewed included prevention and management of aspiration, airway mucus clearance and chest physical therapy, viral respiratory infections, precautions during high altitude or air-flight travel, non-invasive ventilation during sleep, antibiotic therapy, steroid therapy, oxygen therapy, gastrostomy tube placement, Nissen fundoplication surgery, scoliosis surgery, tracheostomy and lung lobectomy. CONCLUSIONS: Expert recommendations for the diagnosis and management of respiratory disease in patients with familial dysautonomia are provided. Frequent reassessment and updating will be needed.

Omalizumab in allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterized by a Th2 response, serum eosinophilia, and increased total serum IgE to Aspergillus fumigatus. ABPA occurs in cystic fibrosis (CF) and asthma. Omalizumab is a humanized recombinant monoclonal antibody against IgE. Previous studies reported borderline results when treating ABPA with omalizumab. METHODS: A retrospective study to investigate the efficacy of omalizumab in the treatment of ABPA in CF patients was conducted at 3 CF centers in Israel and Belgium. Data were obtained from the digital archive. We measured 4 outcome parameters: forced expiratory volume in 1 second, body mass index, pulmonary exacerbations, and steroid sparing. RESULTS: The database was composed on the records of 9 patients. None of the outcome parameters showed any improvement. A favorable outcome was observed in patients with higher levels of posttreatment total IgE than those with lower levels. CF-related diabetes and male gender showed trends for poorer outcomes. CONCLUSION: No benefits were detected on treating ABPA in CF with omlaizumb. Monitoring the total IgE was not helpful. A prospective randomized double-blind study is needed.

Ivacaftor for the p.Ser549Arg (S549R) gating mutation - The Israeli experience.

BACKGROUND: Ivacaftor is a drug that increases the probability of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel remaining open. Information about the efficacy of ivacaftor in patients carrying the rare p.Ser549Arg (S549R) CFTR mutation is sparse. AIM: Efficacy of ivacaftor treatment in patients carrying the p.Ser549Arg (S549R) CFTR mutation. METHODS: Data obtained from CF patients receiving ivacaftor for one year. RESULTS: Eight CF patients, mean age 21 ± 10 years, received ivacaftor. After one year, significant improvement was found in FEV1, increasing from 74% to 88% (p < 0.001), FVC, 89% to 101% (p = 0.019), and FEF25-75, 59%-76% (p = 0.019). Sweat chloride concentration decreased from 116 ± 8 mmol/L to 51 ± 17 mmol/L (p < 0.001), and BMI increased from 20 ± 3 to 22 ± 4 (p = 0.003). Glucose tolerance improved in five patients. There was no significant change in bacterial colonization. CONCLUSIONS: Ivacaftor therapy resulted in significant clinical improvement in patients carrying the p.Ser549Arg (S549R) CFTR mutation.

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening.

BACKGROUND: Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan-population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients. METHODS: An Israeli nationwide genotyping of 152 CF cases, representing 176 patients lacking molecular diagnosis, was conducted. Molecular analysis included Sanger sequencing for all exons and splice sites, multiplex ligation probe amplification (MLPA), and next-generation sequencing of the poly-T/TG tracts. RESULTS: We identified 54 different mutations, of which only 16 overlapped the 22 mutations included in the Israeli preconception screening program. A total of 29/54 (53.7%) mutations were already listed as CF causing by the CFTR2 database, and only 4/54 (7.4%) were novel. Molecular diagnosis was reached in 78/152 (51.3%) cases. Prenatal diagnosis of 24/78 (30.8%) cases could have been achieved by including all CFTR2-causing mutations in the Israeli panel. CONCLUSIONS: Our data reveal an overwhelming hidden abundance of CFTR gene mutations suggesting that expanded preconception carrier screening might achieve higher preconception detection rates.

Consequences of Expiratory Flow Limitation at Rest in Subjects with Cystic Fibrosis.

RATIONALE: Expiratory flow limitation at resting tidal volume (EFLTV) presents a severe mechanical constraint in chronic lung diseases and has not yet been studied longitudinally in cystic fibrosis. OBJECTIVES: To study the effect of EFLTV as it emerged from simple spirometry on lung function and clinical status in cystic fibrosis. METHODS: Best year spirometry that included tidal flow/volume curves and the related clinical data were retrospectively collected over 12 ± 3.0 yr/person from 108 subjects with cystic fibrosis. The year in which forced expiratory flow, midexpiratory phase (FEF25-75%, L/s) was equal to tidal peak expiratory flow (L/s) was defined as EFLTV-onset year. MEASUREMENTS AND MAIN RESULTS: EFLTV occurred in 55 (51%) subjects, at age 23 ± 6 years. At EFLTV onset, tidal peak expiratory flow and FEF25-75% values were 1.44 ± 0.23 L/s and FEV1 was 62 ± 10% predicted. Within the following 2 years, FEV1 dropped to 48 ± 11% predicted, and 35 (63%) of the subjects reported shortness of breath at rest. Hospital days increased from 5.3 ± 24.6 to 24.12 ± 9.0 d/yr (P = 0.0001). Of the 55 subjects, 29 (53%) received transplant or died, with survival time being 6.9 ± 3.9 years. CONCLUSIONS: EFLTV onset may be an important pathophysiological event that could influence the natural history of lung function decline in subjects with cystic fibrosis. This may lead to a significant deterioration in lung function in the following 2 years alongside an increase in the number of hospitalization days. The monitoring of FEV1 alone does not offer as good a threshold signal, because values are only moderately reduced. Therefore, identifying EFLTV appearance is potentially a signal for therapeutic intervention. Further studies are warranted to confirm our findings.

Several siblings with Cystic Fibrosis as a risk factor for poor outcome.

BACKGROUND: Occurrence of Cystic Fibrosis (CF) in more than one member in a family is not uncommon. The aim of our study was to assess the influence of multiple siblings with CF on disease expression and outcome. METHODS: Study group consisted of 2-siblings (2-sibs, n = 42) or 3/4 siblings (3/4-sibs, n = 22) with CF in one family. Each sibling was matched by age, mutation, and gender to a single CF patient. RESULTS: 3/4-sibs subgroup compared to singles showed a lower mean FEV1 with a faster decline rate (58.4 ± 27.5 vs. 72.7 ± 25.4 and -5 ± 6.4 vs. -1.7 ± 2.8 %predicted decline/year respectively, p < .05), more airway colonization by Pseudomonas aeruginosa and Mycobacterium abscessus (15 (68%) vs. 8 (36%) and 7 (32%) vs. 4 (18%), respectively, p < .05) and more lung transplants (5 (23%) vs. 2 (9%), respectively, p < .02). Last mean FEV1 within 3/4-sibs was significantly lower for the youngest sib (p < .05). CONCLUSIONS: Three or more CF patients in one family may be a risk factor for more severe disease and poor prognosis. In our view this reflects the burden of disease on the patients and families.