The impact of pneumococcal conjugate vaccine on the prevalence and severity of hospitalizations for pneumonia in children.

Pneumococcal conjugate vaccines (PCV) were introduced into the Israeli national immunization plan starting with the heptavalent PCV7 in 2009 and then PCV13 in the late 2010. The objective of this study was to determine the vaccines' impact on hospitalization rates for community-acquired pneumonia on the severity of the pneumonia episodes and upon pneumococcal serotype distribution. We retrospectively reviewed all children hospitalized in our institution with pneumonia, aged between 1 and 16 years, between the years 2006 and 2015. Demographic, clinical, and laboratory data between three time periods: pre-PCV, PCV7, and PCV13, were compared. During the study period, 1375 children were hospitalized with pneumonia. A gradual decline in hospitalization rates due to pneumonia was observed starting in 2006 in the pre-PCV period and continued until after the introduction of PCV13. A similar trend was observed in pneumonias with a culture positive for S. pneumoniae. Pleural effusion was observed in 24% of all pneumonias, and this percentage was stable throughout the study period. The average age at hospitalization increased during the study period, as did the average duration of hospital stay. Pneumococcal serotypes included in the vaccine were isolated less frequently during the study and non-vaccine serotypes tended to appear more frequently. Pediatric pneumonia hospitalization rates continued to decline since the introduction of PCV without increasing the frequency of complications. Pneumococcal serotype distribution shifted in parallel. Our findings confirm the efficacy of PCV and support the evidence to include more serotypes in the next generation of PCV.

Being overweight and born in the spring are associated with an increased risk for rhinitis.

AIM: To explore the relationship between the season of birth and the prevalence of recurrent or chronic rhinitis (rhinitis). METHODS: The medical records of consecutive 17-year-old conscripts to the Israeli army were reviewed. We compared the prevalence of rhinitis between children born during different seasons. Multivariate analysis was performed with additional variables. RESULTS: The prevalence of rhinitis among the 1.1 million recruits was 7.1% in males and 5.3% in females. The association between birth season and the prevalence of rhinitis was highly significant (p < 0.001 for both genders). Spring was the birth season with the highest prevalence of rhinitis (7.4% in males and 5.5% in females). Males born in the winter and females born in the autumn had the lowest prevalence of rhinitis (6.7%, and 5.2% respectively). There was an increased odds ratio for rhinitis among those with a body mass index above 25, higher cognitive score and maternal birth country out of Israel or Africa. CONCLUSIONS: There was an increased risk of rhinitis among young Israeli adults who were born in the spring, were overweight and had a higher cognitive-score. Family planning to avoid a spring birth and preventing overweight may reduce the risk of chronic rhinitis.

The influence of reducing fever on blood oxygen saturation in children.

Laboratory-based studies on the oxyhemoglobin dissociation curve (ODC) suggest that high blood temperature decreases the affinity of hemoglobin for oxygen. The aim of the study was to evaluate the influence of pyrexia on oxygen saturation (SpO2) in children presenting to the emergency department. Normoxemic children with body temperature at or above 38.5 °C were included. Patients with a dynamic respiratory disease were excluded. SpO2 was measured before and after antipyretic treatment. The changes in body temperature and SpO2 were assessed and compared to the changes predicted from the ODC. Thirty-four children completed the study. Mean temperature at presentation was 39.17 ± 0.549 °C and mean SpO2 was 96.15 ± 2.21%. The mean decrease in temperature after antipyretic treatment was 1.71 ± 0.67 °C and mean increase in SpO2 was 0.95 ± 1.76%. Among children in whom pyrexia decreased by 1.5 °C or more, the mean increase in SpO2 was 1.45 ± 1.57%. The measured increase in SpO2 was close to the increase anticipated from the ODC. CONCLUSION: Pyrexia was associated with decreased SpO2 in normoxemic children. The influence of pyrexia in children with low-normal oxygen saturation is expected to be much higher because of the non-linear shape of the ODC. Physicians treating patients with fever should be aware of this effect, especially in patients with borderline hypoxia. What is Known: • High blood temperature decreases the affinity of oxygen to hemoglobin. • It is not known whether fever would decrease SpO 2 . What is New: • Fever is associated with decreased SpO 2 .

Is obstructive sleep apnea syndrome in children season dependent?

INTRODUCTION: The most common cause of obstructive sleep apnea (OSA) in children is an enlargement of tonsils and/or adenoids. Previous studies have shown that the size of adenoids and tonsils is influenced by upper respiratory tract infections and exposure to allergens. The rate of exposure to bacteria, viruses, and allergens fluctuates from season to season. Therefore, we hypothesized that the rate of polysomnograms positive for OSA may vary according to season. OBJECTIVE: The objective of this study is to determine whether the prevalence of OSA in children, as determined by polysomnography, is affected by the season during which the study was performed. METHODS: We retrospectively reviewed polysomnography tests of 296 children, ages 0-12 years, referred for suspected OSA. We compared the Obstructive Apnea Hypopnea Index (OAHI) between the seasons and the rates of abnormal tests in each season according to the degree of severity. RESULTS: The mean OAHI did not significantly differ among the seasons (winter, 3.0 ± 5.0; spring, 3.0 ± 4.9; summer, 4.0 ± 6.3; fall, 3.4 ± 5.7, p = 0.183). When dividing the OAHI by levels of severity, no seasonality was found in moderate (winter, 13.8 %; spring, 6.7 %; summer, 11.7 %; fall, 14.1 %, p = NS) and severe OSA (winter, 8.8 %; spring, 11.2 %; summer, 10 %; fall, 7.8 %, p = NS). There was a small increase in the frequency of mild OSA diagnoses in the summer compared to the other seasons. CONCLUSION: In this study, season does not appear to affect the rate of diagnosis of significant OSA in children. Re-evaluation during a different season is unlikely to provide different results and may postpone surgery unnecessarily.

Decline in asthma prevalence and severity in Israel over a 10-year period.

BACKGROUND: The prevalence of asthma has increased in western countries towards the end of the last century, but recently seems to have stabilized. OBJECTIVE: To evaluate trends in the prevalence and severity of asthma that occurred in Israel over the past decade. METHODS: The medical records of 17-year-old boys, eligible for national service, between 1999 and 2008 were reviewed. National annual hospitalization and death rates for asthma were extracted. RESULTS: Three hundred thousand medical records were reviewed. During the study period, lifetime asthma prevalence decreased from 9.7 to 8.1% (p = 0.002). The point prevalence of moderate-to-severe and mild persistent asthma decreased significantly from 0.88 and 3.41% to 0.36 and 2.44%, respectively, during this period. The prevalence of intermittent asthma and asthma in clinical remission for more than 3 years did not change significantly. The annual hospitalization rate for asthma decreased from 13.0 to 7.5 per 10,000 population (p < 0.0001), whilst the annual death rate due to asthma decreased between 1999 and 2008 from 2.1 to 1.4 per 100,000 population (p = 0.003). CONCLUSIONS: The prevalence of asthma in Israeli teenage boys decreased significantly over the last decade. In addition, asthma hospitalization and asthma-related death rates in the total population also decreased.

[Foreign body aspiration in children].

Foreign body (FB) aspiration occurs mainly in children under 3 years of age and is one of the most frequent causes of accidental death under 12 months of age. The increased risk of FB aspiration in children is due to the different structure of the pharynx and the upper airways compared to adults. In addition, children have an immature swallowing mechanism and they most commonly aspirate food stuffs. FB aspiration is usually a sudden and dramatic event when the child feels that he is suffocating or choking. After the acute event, the clinical presentation widely ranges from severe respiratory distress to the most minimal symptoms. Bronchoscopy is the best diagnostic and therapeutic modality for FB inhalation. Prevention and rapid diagnosis can be lifesaving. In 2010, the American Academy of Pediatrics published a position paper on prevention of FB aspiration. The association calls for more proactive preventative measures to protect children from FB aspiration and to prevent mortality and morbidity. These include: 1. Raising awareness of parents and caregivers to supervise children and create a safe environment for them. 2. Promoting legislation and enforcing regulations that will prevent dangerous products being sold for children. 3. Changing the design of products, especially food products and toys, that will reduce the risks of choking. In this overview we will show the principles of diagnosis of FB aspiration and a flow chart including when flexible or rigid bronchoscopy is required.

[The effect of fever on blood oxygen saturation in children].

INTRODUCTION: Blood temperature is inversely correlated with oxygen-hemoglobin affinity as demonstrated by in-vitro oxyhemoglobin dissociation curve (ODC) experimentation. OBJECTIVE: To evaluate the real-life effect of fever on blood oxygen saturation (SO2) in children. METHODS: Children treated in the Pediatric Emergency Department at the "Shaare Zedek" Medical Center with a body temperature > 38.50C were included in the study. Children suffering from active lung disease were excluded. The following parameters were collected before and 90 minutes after administering antipyretic therapy: temperature, SO2, respiratory rate and pulse rate. RESULTS: Twenty-two subjects completed the study. The mean decrease in temperature was 2.030C. Following the decrease in body temperature, a rise in SO2 was noted in 17 subjects (77.3%). The mean SO2 before the antipyretic therapy was 96.18%. The mean SO2 after the drug administration was 97.73%. The average rise in SO2 was 1.55 ± 1.79% (p = 0.001). CONCLUSIONS: Fever in children is associated with decreased SO2. This decrease is not clinically significant in patients with normal baseline SO2. Calculation reveals that in patients with baseline SO2 close to the steep region of the ODC, the same increase of body temperature will cause a significantly greater decrease in SO2. In patients with a baseline SO2 of 91% at body temperature of 370.00C, an increase in body temperature to 400.00C is anticipated to cause a 5% decrease in SO2. This decrease has major potential implications concerning treatment decisions.

Methacholine challenge test results in children are season dependent.

BACKGROUND: It is known that several parameters influence the positivity of a methacholine challenge (MCH), including a recent viral disease, allergies, and air pollution. Reports regarding the influence of the season upon the positivity of MCH are scarce. The aim of this study was to assess the percentage of positive MCH tests per season. METHODS: We retrospectively evaluated all MCH tests performed in children and adults in a single center over a 30-month period. The percentage of positive tests for summer was compared with that of other seasons. RESULTS: A total of 155 challenges were performed in children (under 20 years old) and 527 in adults. Thirty-eight percent of the tests were positive in adults and 71 % in children. The percentage of positive tests in the summer was significantly lower than the percentage of positive results during the rest of the year in children (58.5 vs. 75.4 %, respectively; p = 0.046). By contrast, there was no difference between the seasons in adults (39 vs. 38 %, respectively; p = 0.92). CONCLUSIONS: There is a difference of 22.4 % in the percentage of positive tests in the summer months compared to the rest of the year in children, suggesting a reduction in the sensitivity of the MCH test in the hot season. We suggest that in cases where asthma is strongly suspected in a child and the MCH test was negative in the summer, one should consider repeating the MCH test in another season.

Ultrasound velocity through the tibia is not affected by prolonged inhaled steroid therapy in children.

AIM: To evaluate in a prospective, cross-sectional cohort study the impact of inhaled corticosteroids (ICS) on bone speed of sound (SOS) in asthmatic children. METHODS: Children with mild-to-moderate asthma from a pulmonary clinic were assessed over a 2-month period. We recorded clinical and demographic data related to asthma severity, its treatment, participation in sports and dairy intake. Tibial SOS was measured using the Sunlight Omnisense 7000S quantitative ultrasound bone sonometer. RESULTS: Eighty-five mild-to-moderate asthmatic children were studied. Age range was 1.4-17 years (71.7% boys). Average disease duration was approximately 5 years, and the average cumulative duration of ICS therapy was approximately 1.5 years. Average SOS Z-score was slightly negative and varied between -3.5 and +1.9 SD. In univariate analysis, SOS Z-score was negatively correlated with asthma duration (R(2) = 5.7%, p = 0.028) and ICS duration (R(2) = 4.9%, p = 0.042). In backward stepwise multiple regression, where SOS Z-score was the dependent variable, the only variables that remained significant in the final analysis were gender (p = 0.015), asthma duration (p = 0.003) and BMI (p = 0.048) (R(2) for the model 17.52% p = 0.01). CONCLUSION: Prolonged inhaled steroid therapy appears to have no deleterious effect upon SOS in children with mild-to-moderate persistent asthma.

Newborn oxygen saturation at mild altitude versus sea level: implications for neonatal screening for critical congenital heart disease.

AIM: To determine the normal SpO2 in healthy term newborns at mild altitude (MA, 780 metres) compared with sea level (SL), within the context of universal screening for critical congenital heart disease (CCHD). METHODS: We studied 199 (119 at MA and 80 at SL) consecutively born healthy newborns. SpO2 recordings were at 24-72 h using Masimo SET Radical-7 on the right hand and left foot. RESULTS: Mean SpO2 was lower at MA compared with SL in the right hand (97.86 ± 1.58 vs 98.28 ± 1.41, p = 0.05) and left foot (98.49 ± 1.35 vs 98.90 ± 1.16, p = 0.03). No infant with SpO2 <95% had CCHD. Extrapolating with predicted regression lines set at 95% CI, a SpO2 cut-off of 95% would result in up to 3.5 times more false-positive screens at MA compared with SL. CONCLUSIONS: At MA, SpO2 is approximately 0.4% lower compared with SL. Our study supports the AAP recommendation suggesting algorithm cut-offs may need adjustment in high-altitude nurseries and suggest broadening it to MA as well.

Asthma and hemoglobinopathy: when is supplemental oxygen required?

Asthma is the most common reason for referral to the emergency department in childhood. In severe attacks, supplemental O2 is given when oxygen saturation level is <90%. Described herein is the case of a child with persistent low oxygen saturation as measured on pulse oximetry (S(p)O2) after full clinical recovery from an asthma attack. Simultaneously, P(a)O2 was normal. A diagnosis of abnormal hemoglobin with decreased oxygen affinity (hemoglobin Seattle) was made on hemoglobin electrophoresis and genetic analysis. To ascertain when supplemental oxygen was needed, an oxygen dissociation curve was plotted using the tonometer technique, and it was found that an S(p)O2 of 70% is parallel to a P(a)O2 of 60 mmHg. Plotting an oxygen dissociation curve is a simple reproducible method to determine when supplemental oxygen is required for a child with a hemoglobinopathy.

Association of the risk of obstructive sleep apnoea with the severity of COVID-19.

Patients with coronavirus 2019 (COVID-19) and obstructive sleep apnoea (OSA) have a worse prognosis than COVID-19 patients without OSA. This study aimed to examine the relationship between OSA risk and the severity of COVID-19 in patients undiagnosed with OSA. Patients diagnosed with COVID-19 and hospitalized or admitted to a community hotel were recruited for the study after recovery during a clinic check-up visit 6-8 weeks after discharge. At this visit, they answered the Epworth Sleeping Scale (ESS) and Berlin questionnaire. Demographic and clinical details were collected from electronic medical records. OSA risk was observed in 37 of 119 included patients (31.1%). Patients with high OSA risk were male, significantly older, had a higher body mass index (BMI), and had higher rates of hypertension and snoring than patients with low OSA risk. Moreover, OSA risk was associated with COVID-19 severity; 48.6% of patients with high risk for OSA suffered from severe COVID-19 compared to 22% of patients with low risk for OSA (p = 0.007). The duration of hospitalization for patients with a high OSA risk was 10.97±9.43 days, while that for those with a low OSA risk was 4.71±6.86 days (p = 0.001). After adjusting for BMI, age, hypertension, and chronic disease, the odds ratio was 4.3 (95%CI, 1.2-16, p = 0.029). A high OSA risk was associated with severe COVID-19 and longer hospitalization. Thus, we recommend that the Berlin and ESS questionnaires be completed for every COVID-19-infected patient at hospitalization, especially in the presence of comorbidities.

SARS-CoV-2 spike antibody concentration in gamma globulin products from high-prevalence COVID-19 countries are transmitted to X-linked agammaglobulinemia patients.

Purpose: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient. Methods: A single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly. Results: Five XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was obtained for 111 (96%) of the treatments. Fifty-four IVIG preparations (49%) were harvested during the COVID-19 pandemic of which 76% were positive (>50AU/mL) for SARS-CoV-2 spike antibodies which were subsequently transmitted to the XLA patients in an approximate 10-fold reduction. SARS-CoV2 spike IgG was first detected in IVIG batches that completed their harvest date by September 2021. Positive products were harvested from origin countries with a documented prevalence over 2,000 per 100,000 population. Conclusion: As the prevalence of COVID-19 infections rises, detection of SARS-CoV-2 spike IgG in commercial IVIG products increases and is then transmitted to the patient. Future studies are needed to investigate the neutralizing capabilities of SARS-CoV-2 IgG and whether titer levels in IVIG remain consistent as the incidence of infection and vaccination rates in the population changes.

Effect of moderate elevation above sea level on blood oxygen saturation in healthy young adults.

BACKGROUND: Arterial hemoglobin oxygen saturation (SaO2) decreases at an altitude of >1,500 m. There are no reports on normal SaO2 at altitudes between 0 and 1,500 m. The clinical significance of decreased SaO2 at such altitudes is unclear. OBJECTIVE: To test the hypothesis that in healthy volunteers normal SaO2 at moderate altitude (MA; 725 m) is lower than that at almost sea level (SL; 43 m). METHODS: SaO2 was measured by transcutaneous pulse oximetry in young healthy volunteers at MA and was compared to equivalent measurements at SL. In addition, a 6-min walk test was performed and SaO2 at the end of the walk was compared between the two locations. RESULTS: 111 males were checked at MA and 101 at SL. At rest, nadir SaO2 was 95% at MA compared to 97% at SL. Mean SaO2 at rest was slightly higher at SL (98.53 ± 0.52) compared to MA (98.11 ± 0.8; p < 0.01). In subjects who completed the 6-min walk test, SaO2 slightly decreased after the test in both locations, by 0.38 ± 0.65% in the SL group and by 0.37 ± 1.12% in the MA group. This difference is not statistically significant by univariate analysis; however, a multiple regression analysis indicated that the drop in SaO2 was higher at MA than at low altitude. CONCLUSIONS: We found a low but significant difference in SaO2 between near-SL and at an altitude of 725 m. The clinical significance of this difference, in terms of human health, is probably minimal.

Seasonal effect on exercise challenge tests for the diagnosis of exercise-induced bronchoconstriction.

Exercise challenge test (ECT) may help in the diagnosis of asthma. Asthma is season dependent (relative summer nadir).This study was designed to prospectively show that ECT sensitivity decreases when performed in summer and/or out of personal asthma season. We performed two ECTs in 49 patients with suspected asthma, at baseline and at least 6 months later. Test positivity was defined as a ≥10% drop of forced expiratory volume in 1 second after exercise. Patients were defined as having exercise-induced bronchoconstriction (EIB) if at least one of the two tests was positive. We analyzed the impact of season and of patient-reported asthma season on ECT sensitivity. We performed 21 ECTs in the summer and 77 in other seasons. Summer tests were positive in 14.3% of patients versus 33.8% in other seasons (p = 0.11). In patients with confirmed EIB, the sensitivity (95% CI) of a summer test was 0.25 (0.007-0.57), compared with 0.76 (0.58-0.89) in other seasons. Tests performed out of personal asthma season were positive in 10.0% of tests compared with 37.1% of tests during personal asthma season (p = 0.007). In patients with confirmed EIB, the sensitivity (95% CI) of a test performed out of asthma season was 0.27 (0.07-0.61), compared with 0.74 (0.55-0.87) during season. The sensitivity of ECT performed in the summer or outside of the personal asthma season is about one-third of ECT performed not in the summer or during personal asthma season. We suggest performing ECTs during personal asthma season and not in the summer if there is no asthma season known.

Factors associated with resolution of childhood asthma by the age of 17: Large cohort analysis.

BACKGROUND: Many children with asthma will become asymptomatic during adolescence. In this study, we evaluated factors associated with recovery from asthma by the age of 17. METHODS: The medical records of 17-year-old conscripts to the Israeli army with asthma were compared with the records of conscripts with rigorously diagnosed resolved asthma. We assessed the association between the following parameters and asthma resolution: body mass index (BMI), recurrent rhinitis, birth season, socioeconomic level, and cognition. RESULTS: Sixty-eight thousand and ninety conscripts with active asthma were compared to 14,695 with resolved asthma. In univariate analysis, rhinitis, overweight, underweight, higher socioeconomic level, and lower cognitive score were associated with active asthma (p < 0.001 for both sexes), but not the season of birth. In multivariate analysis, only overweight, underweight, rhinitis, and lower cognitive score (p < 0.001 for both sexes) remained significantly associated with persistence of asthma. CONCLUSIONS: Although association does not prove causation, our finding is another reason to encourage adolescents with asthma to maintain a normal body weight. Prospective interventional studies are needed in order to decide whether changing weight to ensure BMI is within the ideal range and controlling rhinitis increases the odds of resolution of asthma in adolescence.

Unilateral lung intubation for pulmonary air leak syndrome in neonates: a case series and a review of the literature.

Air leak syndrome represents a common set of complications of ventilated premature neonates and includes pneumothorax, pneumomediastinum, pulmonary interstitial emphysema, and pneumatocele. Unilateral intubation is an infrequently utilized treatment option. We report our experience of three cases of air leak syndrome in neonates, each treated with unilateral intubation, including two cases of recalcitrant pneumothorax. A review of the literature of similar neonatal cases is presented. In view of our experience and the review of the literature, we suggest that unilateral intubation is an efficient and relatively safe therapy in cases of neonatal air leak syndrome. It is also suggested that appropriate treatment duration should be at least 48 hours.

Absence of leukocytosis in bacteraemic pneumococcal pneumonia.

BACKGROUND: Evaluation of patients with respiratory symptoms in primary care medicine is often based on peripheral WBC count that dictates the extent of diagnostic investigation. A normal WBC count may result in a limited investigation, often omitting chest radiography. AIMS: To determine the extent to which patients hospitalised with bacteraemic pneumococcal pneumonia have no leukocytosis at presentation. METHODS: A retrospective analysis was performed of patients with bacteraemic community-acquired pneumococcal pneumonia from 2000 to 2007 in a community care academic medical centre. Records were reviewed for symptoms, signs, and laboratory data including pneumococcal serotypes, chest radiographs on admission, and outcome. RESULTS: 21% of the patients presented with a normal WBC count (16.7% of the children and 25.6% of the adults). Among this population with a normal WBC count at presentation, 90% of the adults and 70% of the children developed leukocytosis within a few days after admission. CONCLUSIONS: In this study, in as many as one-fifth of all the patients with bacteraemic pneumococcal pneumonia, there was no leukocytosis at presentation. We therefore suggest that every patient with clinically suspected pneumonia should undergo chest radiography even if the WBC count is normal.

Are there gender differences in blood oxygen saturation in prepubertal children?

INTRODUCTION: Previous studies reported higher oxygen saturation (SpO2 ) in healthy young adult females as compared to males. The objective of the current study was to evaluate whether or not similar differences exist in prepubertal children. METHODS: SpO2 levels, respiratory rate, and pulse were measured in 4- to 10-year-old males and females. Anthropometric variables, including ethnic origin, age, height, weight, BMI (Body Mass Index), BSA (Body Surface Area), barometric pressure, and altitude above sea level were collected as well. RESULTS: Ninety five males and 93 females participated in the study. Groups were similar, in terms of respiratory rate, pulse, and anthropometric variables. Mean SpO2 in males was 96.95 ± 1.09%, similar to SpO2 in females measuring 96.85 ± 0.98%, P = .52. CONCLUSION: In contrast to young adults, there is no gender-related difference in mean oxygen saturation in prepubertal healthy children. It is likely that this difference is due to variations in age-related sex hormones. Further studies are needed to explore the mechanism explaining why prepubertal children do not show gender-specific differences in oxygen saturation in contrast to adults.