Lack of Biological Plausibility and Major Methodological Issues Cast Doubt on the Association between Aspartame and Autism. Comment on Fowler et al. Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study. Nutrients 2023, 15, 3772.

The case-control study by Fowler et al [...].

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.

Rationale, Design and Participants Baseline Characteristics of a Crossover Randomized Controlled Trial of the Effect of Replacing SSBs with NSBs versus Water on Glucose Tolerance, Gut Microbiome and Cardiometabolic Risk in Overweight or Obese Adult SSB Consumer: Strategies to Oppose SUGARS with Non-Nutritive Sweeteners or Water (STOP Sugars NOW) Trial and Ectopic Fat Sub-Study.

BACKGROUND: Health authorities are near universal in their recommendation to replace sugar-sweetened beverages (SSBs) with water. Non-nutritive sweetened beverages (NSBs) are not as widely recommended as a replacement strategy due to a lack of established benefits and concerns they may induce glucose intolerance through changes in the gut microbiome. The STOP Sugars NOW trial aims to assess the effect of the substitution of NSBs (the "intended substitution") versus water (the "standard of care substitution") for SSBs on glucose tolerance and microbiota diversity. DESIGN AND METHODS: The STOP Sugars NOW trial (NCT03543644) is a pragmatic, "head-to-head", open-label, crossover, randomized controlled trial conducted in an outpatient setting. Participants were overweight or obese adults with a high waist circumference who regularly consumed ≥1 SSBs daily. Each participant completed three 4-week treatment phases (usual SSBs, matched NSBs, or water) in random order, which were separated by ≥4-week washout. Blocked randomization was performed centrally by computer with allocation concealment. Outcome assessment was blinded; however, blinding of participants and trial personnel was not possible. The two primary outcomes are oral glucose tolerance (incremental area under the curve) and gut microbiota beta-diversity (weighted UniFrac distance). Secondary outcomes include related markers of adiposity and glucose and insulin regulation. Adherence was assessed by objective biomarkers of added sugars and non-nutritive sweeteners and self-report intake. A subset of participants was included in an Ectopic Fat sub-study in which the primary outcome is intrahepatocellular lipid (IHCL) by 1H-MRS. Analyses will be according to the intention to treat principle. BASELINE RESULTS: Recruitment began on 1 June 2018, and the last participant completed the trial on 15 October 2020. We screened 1086 participants, of whom 80 were enrolled and randomized in the main trial and 32 of these were enrolled and randomized in the Ectopic Fat sub-study. The participants were predominantly middle-aged (mean age 41.8 ± SD 13.0 y) and had obesity (BMI of 33.7 ± 6.8 kg/m2) with a near equal ratio of female: male (51%:49%). The average baseline SSB intake was 1.9 servings/day. SSBs were replaced with matched NSB brands, sweetened with either a blend of aspartame and acesulfame-potassium (95%) or sucralose (5%). CONCLUSIONS: Baseline characteristics for both the main and Ectopic Fat sub-study meet our inclusion criteria and represent a group with overweight or obesity, with characteristics putting them at risk for type 2 diabetes. Findings will be published in peer-reviewed open-access medical journals and provide high-level evidence to inform clinical practice guidelines and public health policy for the use NSBs in sugars reduction strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03543644.

Are all fibres created equal with respect to lipid lowering? Comparing the effect of viscous dietary fibre to non-viscous fibre from cereal sources: a systematic review and meta-analysis of randomised controlled trials.

Although compelling evidence from observational studies supports a positive association between consumption of cereal fibre and CVD risk reduction, randomised controlled trials (RCT) often target viscous fibre type as the prospective contributor to lipid lowering to reduce CVD risk. The objective of our study is to compare the lipids-lowering effects of viscous dietary fibre to non-viscous, cereal-type fibre in clinical studies. RCT that evaluated the effect of viscous dietary fibre compared with non-viscous, cereal fibre on LDL cholesterol and alternative lipid markers, with a duration of ≥ 3 weeks, in adults with or without hypercholesterolaemia were included. Medline, EMBASE, CINAHL and the Cochrane Central Register were searched through October 19, 2021. Data were extracted and assessed by two independent reviewers. The generic inverse variance method with random effects model was utilised to pool the data which were expressed as mean differences (MD) with 95 % CI. Eighty-nine trials met eligibility criteria (n 4755). MD for the effect of viscous dietary fibre compared with non-viscous cereal fibre were LDL cholesterol (MD = -0·26 mmol/l; 95 % CI: -0·30, -0·22 mmol/l; P < 0·01), non-HDL cholesterol (MD = -0·33 mmol/l; 95 % CI: -0·39, -0·28 mmol/l; P < 0·01) and Apo-B (MD = -0·04 g/l; 95 % CI: -0·06, -0·03 g/l; P < 0·01). Viscous dietary fibre reduces LDL cholesterol and alternative lipid markers relative to the fibre from cereal sources, hence may be a preferred type of fibre-based dietary intervention targeting CVD risk reduction.

Body fat and risk of all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND/OBJECTIVES: We aimed to evaluate the relationships between body fat percentage (BF%), fat mass (FM), fat mass index (FMI) and visceral (VAT) and subcutaneous adipose tissue (SAT) with risk of all-cause mortality. METHODS: We did a systematic search in PubMed, Scopus, and Web of Science to June 2021. We selected prospective cohorts of the relationship between body fat with risk of all-cause mortality in the general population. We applied random-effects models to calculate the relative risks (RRs) and 95%CIs. RESULTS: A total of 35 prospective cohort studies with 923,295 participants and 68,389 deaths were identified. The HRs of all-cause mortality for a 10% increment in BF were 1.11 (95%CI: 1.02, 1.20; I2 = 93%, n = 11) in the general adult populations, and 0.92 (95%CI: 0.79, 1.06; I2 = 76%, n = 7) in adults older than 60 years. The HRs were 1.06 (95%CI: 1.01, 1.12; I2 = 86%, n = 10) for a 5 kg increment in FM, 1.11 (95%CI: 1.06, 1.16; I2 = 79%, n = 7) for a 2 kg/m2 increment in FMI, and 1.17 (95%CI: 1.03, 1.33; I2 = 72%, n = 8) and 0.81 (0.66, 0.99; I2 = 59%, n = 6) for a 1-SD increment in VAT and SAT, respectively. There was a J shaped association between BF% and FM and all-cause mortality risk, with the lowest risk at BF% of 25% and FM of 20 kg. In subgroup analyses, although there was little evidence of between-subgroup heterogeneity, the observed positive associations were more pronounced in studies which had a longer duration, excluded participants with prevalent cardiovascular disease and cancer at baseline, with adjustment for smoking or restricted to never smokers, and less pronounced in studies which adjusted for potential intermediates, suggesting an impact of reverse causation, confounding and over-adjustment in some of the studies. CONCLUSIONS: Higher body fat content was related to a higher risk of mortality in a J shaped manner. Any future studies should further assess the impact of reverse causation and residual confounding on these associations. REGISTRATION: PROSPERO (CRD42021240743).

Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis.

Importance: There are concerns that low- and no-calorie sweetened beverages (LNCSBs) do not have established benefits, with major dietary guidelines recommending the use of water and not LNCSBs to replace sugar-sweetened beverages (SSBs). Whether LNCSB as a substitute can yield similar improvements in cardiometabolic risk factors vs water in their intended substitution for SSBs is unclear. Objective: To assess the association of LNCSBs (using 3 prespecified substitutions of LNCSBs for SSBs, water for SSBs, and LNCSBs for water) with body weight and cardiometabolic risk factors in adults with and without diabetes. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception through December 26, 2021. Study Selection: Randomized clinical trials (RCTs) with at least 2 weeks of interventions comparing LNCSBs, SSBs, and/or water were included. Data Extraction and Synthesis: Data were extracted and risk of bias was assessed by 2 independent reviewers. A network meta-analysis was performed with data expressed as mean difference (MD) or standardized mean difference (SMD) with 95% CIs. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to assess the certainty of the evidence. Main Outcomes and Measures: The primary outcome was body weight. Secondary outcomes were other measures of adiposity, glycemic control, blood lipids, blood pressure, measures of nonalcoholic fatty liver disease, and uric acid. Results: A total of 17 RCTs with 24 trial comparisons were included, involving 1733 adults (mean [SD] age, 33.1 [6.6] years; 1341 women [77.4%]) with overweight or obesity who were at risk for or had diabetes. Overall, LNCSBs were a substitute for SSBs in 12 RCTs (n = 601 participants), water was a substitute for SSBs in 3 RCTs (n = 429), and LNCSBs were a substitute for water in 9 RCTs (n = 974). Substitution of LNCSBs for SSBs was associated with reduced body weight (MD, -1.06 kg; 95% CI, -1.71 to -0.41 kg), body mass index (MD, -0.32; 95% CI, -0.58 to -0.07), percentage of body fat (MD, -0.60%; 95% CI, -1.03% to -0.18%), and intrahepatocellular lipid (SMD, -0.42; 95% CI, -0.70 to -0.14). Substituting water for SSBs was not associated with any outcome. There was also no association found between substituting LNCSBs for water with any outcome except glycated hemoglobin A1c (MD, 0.21%; 95% CI, 0.02% to 0.40%) and systolic blood pressure (MD, -2.63 mm Hg; 95% CI, -4.71 to -0.55 mm Hg). The certainty of the evidence was moderate (substitution of LNCSBs for SSBs) and low (substitutions of water for SSBs and LNCSBs for water) for body weight and was generally moderate for all other outcomes across all substitutions. Conclusions and Relevance: This systematic review and meta-analysis found that using LNCSBs as an intended substitute for SSBs was associated with small improvements in body weight and cardiometabolic risk factors without evidence of harm and had a similar direction of benefit as water substitution. The evidence supports the use of LNCSBs as an alternative replacement strategy for SSBs over the moderate term in adults with overweight or obesity who are at risk for or have diabetes.

Dietary carbohydrate and the risk of type 2 diabetes: an updated systematic review and dose-response meta-analysis of prospective cohort studies.

We did this study to clarify the association between carbohydrate intake and the risk of type 2 diabetes (T2D) and potential effect modification by geographical location. PubMed, Scopus and Web of Science were searched to find prospective cohort studies of dietary carbohydrate intake and T2D risk. A random-effects dose-response meta-analysis was performed to calculate the summary hazard ratios (HRs) and 95%CIs. The quality of cohort studies and the certainty of evidence was rated using the Newcastle-Ottawa Scale and GRADE tool, respectively. Eighteen prospective cohort studies with 29,229 cases among 607,882 participants were included. Thirteen studies were rated to have high quality, and five as moderate quality. The HR for the highest compared with the lowest category of carbohydrate intake was 1.02 (95%CI: 0.91, 1.15; I2 = 67%, GRADE = low certainty). The HRs were 0.93 (95%CI: 0.82, 1.05; I2 = 58%, n = 7) and 1.26 (95%CI: 1.11, 1.44; I2 = 6%, n = 6) in Western and Asian countries, respectively. Dose-response analysis indicated a J shaped association, with the lowest risk at 50% carbohydrate intake (HR50%: 0.95, 95%CI: 0.90, 0.99) and with risk increasing significantly at 70% carbohydrate intake (HR70%: 1.18, 95%CI: 1.03, 1.35). There was no association between low carbohydrate diet score and the risk of T2D (HR: 1.14, 95%CI: 0.89, 1.47; I2 = 90%, n = 5). Carbohydrate intake within the recommended 45-65% of calorie intake was not associated with an increased risk of T2D. Carbohydrate intake more than 70% calorie intake might be associated with a higher risk.

Mediterranean dietary pattern and bone mineral density: a systematic review and dose-response meta-analysis of observational studies.

BACKGROUND: We aimed to systematically review the literature and test the dose-response relationship between adherence to the Mediterranean diet (MedDiet) and values of bone mineral density (BMD) in adults. METHODS: Relevant observational studies were selected through searching PubMed, Scopus, and Web of Science databases up to March 4, 2021. A random-effects dose-response meta-analysis was performed to estimate the change in total and regional-specific BMD for a 2-point increment in the score of adherence to the MedDiet, and to clarify the shape of these associations. RESULTS: Seven cross-sectional and one cohort studies with a total number of 13,209 participants were included in the final analyses. Each 2-point increment in the score of adherence to the MedDiet was associated with 0.009 (95% CI: 0.002, 0.016; I2 = 34%, n = 7), 0.006 (95% CI: 0.001, 0.012; I2 = 34%, n = 7), 0.005 (95% CI: 0.003, 0.007; I2 = 1%, n = 4), 0.005 (95% CI: 0.002, 0.008; I2 = 0%, n = 3), and 0.007 (95% CI: 0.005, 0.009; I2 = 0%, n = 4) gr/cm2 higher BMD of lumbar spine, femoral neck, hip, trochanter, and whole body, respectively. There was a positive linear relationship between the MedDiet adherence score and BMD of hip and trochanter. A nonlinear relationship was seen for lumbar spine, femoral neck, and whole body, with sharper increase in the BMD at lower MedDiet scores. The associations remained significant after controlling for important confounders including body weight, physical activity, smoking status, and energy intake. CONCLUSION: Greater adherence to the MedDiet was associated with a small but important increase in BMD at the lumbar spine, femoral neck, hip, trochanter, and whole body. Adopting a Mediterranean-style eating pattern may have modest beneficial effects on bone health.

Different Food Sources of Fructose-Containing Sugars and Fasting Blood Uric Acid Levels: A Systematic Review and Meta-Analysis of Controlled Feeding Trials.

BACKGROUND: Although fructose as a source of excess calories increases uric acid, the effect of the food matrix is unclear. OBJECTIVES: To assess the effects of fructose-containing sugars by food source at different levels of energy control on uric acid, we conducted a systematic review and meta-analysis of controlled trials. METHODS: MEDLINE, Embase, and the Cochrane Library were searched (through 11 January 2021) for trials ≥ 7 days. We prespecified 4 trial designs by energy control: substitution (energy-matched replacement of sugars in diets); addition (excess energy from sugars added to diets); subtraction (energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced in diets) designs. Independent reviewers (≥2) extracted data and assessed the risk of bias. Grading of Recommendations, Assessment, Development, and Evaluation was used to assess the certainty of evidence. RESULTS: We included 47 trials (85 comparisons; N = 2763) assessing 9 food sources [sugar-sweetened beverages (SSBs), sweetened dairy, fruit drinks, 100% fruit juice, fruit, dried fruit, sweets and desserts, added nutritive sweetener, and mixed sources] across 4 energy control levels in predominantly healthy, mixed-weight adults. Total fructose-containing sugars increased uric acid levels in substitution trials (mean difference, 0.16 mg/dL;  95% CI:  0.06-0.27 mg/dL;  P = 0.003), with no effect across the other energy control levels. There was evidence of an interaction by food source: SSBs and sweets and desserts increased uric acid levels in the substitution design, while SSBs increased and 100% fruit juice decreased uric acid levels in addition trials. The certainty of evidence was high for the increasing effect of SSBs in substitution and addition trials and the decreasing effect of 100% fruit juice in addition trials and was moderate to very low for all other comparisons. CONCLUSIONS: Food source more than energy control appears to mediate the effects of fructose-containing sugars on uric acid. The available evidence provides reliable indications that SSBs increase and 100% fruit juice decreases uric acid levels. More high-quality trials of different food sources are needed. This trial was registered at clinicaltrials.gov as NCT02716870.

Central fatness and risk of all cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies.

OBJECTIVE: To quantify the association of indices of central obesity, including waist circumference, hip circumference, thigh circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, with the risk of all cause mortality in the general population, and to clarify the shape of the dose-response relations. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed and Scopus from inception to July 2019, and the reference lists of all related articles and reviews. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies reporting the risk estimates of all cause mortality across at least three categories of indices of central fatness. Studies that reported continuous estimation of the associations were also included. DATA SYNTHESIS: A random effects dose-response meta-analysis was conducted to assess linear trend estimations. A one stage linear mixed effects meta-analysis was used for estimating dose-response curves. RESULTS: Of 98 745 studies screened, 1950 full texts were fully reviewed for eligibility. The final analyses consisted of 72 prospective cohort studies with 2 528 297 participants. The summary hazard ratios were as follows: waist circumference (10 cm, 3.94 inch increase): 1.11 (95% confidence interval 1.08 to 1.13, I2=88%, n=50); hip circumference (10 cm, 3.94 inch increase): 0.90 (0.81 to 0.99, I2=95%, n=9); thigh circumference (5 cm, 1.97 inch increase): 0.82 (0.75 to 0.89, I2=54%, n=3); waist-to-hip ratio (0.1 unit increase): 1.20 (1.15 to 1.25, I2=90%, n=31); waist-to-height ratio (0.1 unit increase): 1.24 (1.12 to 1.36, I2=94%, n=11); waist-to-thigh ratio (0.1 unit increase): 1.21 (1.03 to 1.39, I2=97%, n=2); body adiposity index (10% increase): 1.17 (1.00 to 1.33, I2=75%, n=4); and A body shape index (0.005 unit increase): 1.15 (1.10 to 1.20, I2=87%, n=9). Positive associations persisted after accounting for body mass index. A nearly J shaped association was found between waist circumference and waist-to-height ratio and the risk of all cause mortality in men and women. A positive monotonic association was observed for waist-to-hip ratio and A body shape index. The association was U shaped for body adiposity index. CONCLUSIONS: Indices of central fatness including waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, independent of overall adiposity, were positively and significantly associated with a higher all cause mortality risk. Larger hip circumference and thigh circumference were associated with a lower risk. The results suggest that measures of central adiposity could be used with body mass index as a supplementary approach to determine the risk of premature death.

Important Food Sources of Fructose-Containing Sugars and Incident Hypertension: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Background Sugar-sweetened beverages are associated with hypertension. We assessed the relation of important food sources of fructose-containing sugars with incident hypertension using a systematic review and meta-analysis of prospective cohort studies. Methods and Results We searched MEDLINE, EMBASE, and Cochrane (through December week 2, 2018) for eligible studies. For each food source, natural log-transformed risk ratios (RRs) for incident hypertension were pooled using pair-wise meta-analysis and linear and nonlinear dose-response meta-analyses. Certainty in our evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. We identified 26 reports, including 15 prospective cohorts (930 677 participants; 363 459 cases). Sugar-sweetened beverages showed harmful (RRper-355-mL, 1.10 [95% CI, 1.08, 1.12]) whereas fruit (RRper-240-g, 0.94 [95% CI, 0.96, 0.99]) and yogurt showed protective associations (RRper-125-g, 0.95 [95% CI, 0.94, 0.97]) with incident hypertension throughout the dose range. One hundred percent fruit juice showed a protective association only at moderate doses (RRat-100-mL, 0.97 [95% CI, 0.94, 0.99]). The pair-wise protective association of dairy desserts was not supported by linear dose-response analysis. Fruit drinks or sweet snacks were not associated with hypertension. Certainty of the evidence was "low" for sugar-sweetened beverages, 100% fruit juice, fruit, and yogurt and "very low" for fruit drinks, sweet snacks, and dairy desserts. Conclusions The harmful association between sugar-sweetened beverages and hypertension does not extend to other important food sources of fructose-containing sugars. Further research is needed to improve our estimates and better understand the dose-response relationship between food sources of fructose-containing sugars and hypertension. Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02702375.

Caries risk assessment using Cariogram model among smokeless tobacco users in India.

BACKGROUND: Smokeless tobacco forms are known to have fermentable sugar compounds which may strengthen the development of cariogenic microbes. In addition, cervical abrasion of teeth occur at the site of tobacco pouch placement. These components may assume an essential role in caries advancement in smokeless tobacco users. OBJECTIVE: The objective of the study was to assess caries risk among smokeless tobacco users using Cariogram model. METHODS: A descriptive cross sectional study was conducted among 50 smokeless tobacco users of Udaipur for 3 months. Caries risk assessment was done by employing a proforma survey based on the Cariogram Model. Statistical analysis included descriptive statistics, Chi-square test and Stepwise multiple linear regression with 95% confidence interval and 5% significance level. RESULTS: The majority of the smokeless tobacco users (46%) were found to be in the "Moderate" Streptococcus mutans count category and portrayed "Moderate" plaque amount score (82%). Smokeless tobacco users (34%) depicted a higher caries risk profile than the control group (6%) utilizing the Cariogram model. CONCLUSION: Cariogram model could be a useful tool to represent caries risk among smokeless tobacco users.

Acute respiratory infections in Pakistan: have we made any progress?

Acute respiratory infections (ARI) are the leading cause of death in young children in Pakistan, responsible for 20-30% of all child deaths under age 5 years. This paper summarizes the research and technical development efforts over the last 15 years which have contributed to improving the effectiveness of the case management strategy to reduce mortality from pneumonia in children in Pakistan. Community intervention is viable, effective and practical. Rising antimicrobial resistance among commonly used and low-cost oral agents is of significant concern. Appropriate monitoring and evaluation of the impact of the ARI control programme is lacking. Lack of funding for programmatic activities, lack of coordination with other child survival programs, inadequate training for community health workers and general practitioners in the private sector, lack of public awareness about seeking timely and appropriate care, and insufficient planning and support for ARI programmatic activities at provincial and district levels are major hindrances in decreasing the burden of ARI in the country. The recent introduction of the community-based Lady Health Worker (LHW) Programme and WHO and UNICEF-sponsored integrated management of childhood illness initiative present ideal opportunities for re-emphasizing early case detection and appropriate case management of ARI. Ultimately, focusing on preventive strategies such as improving nutrition, reducing indoor pollution, improving mass vaccination, as well as introduction of new vaccines effective against important respiratory pathogens will likely have the most impact on reducing severe ARI and deaths from severe disease.