The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and may be important in the development and progression of non–small cell lung cancer (NSCLC). We examined the impact of EGFR–tyrosine kinase inhibitors (TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with and without EGFR mutations. Randomized trials that compared EGFR-TKIs monotherapy or combination EGFR-TKIs-chemotherapy with chemotherapy or placebo were included. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs for the EGFR mutation–positive (EGFRmut⁺) and EGFR mutation–negative (EGFRmut^–) subgroups were calculated with the fixed-effects inverse variance weighted method. All statistical tests were two-sided. We included 23 eligible trials (13 front-line, 7 second-line, 3 maintenance; n = 14570). EGFR mutation status was known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut⁺ patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut⁺ was 0.43 (95% confidence interval [CI] = 0.38 to 0.49; P < .001), and the front-line hazard ratio for EGFRmut^– was 1.06 (95% CI = 0.94 to 1.19; P = .35; P_interaction < .001). The second-line hazard ratio for EGFRmut⁺ was 0.34 (95% CI = 0.20 to 0.60; P < .001), and the second-line hazard ratio for EGFRmut^– was 1.23 (95% CI = 1.05 to 1.46; P = .01; P_interaction < .001). The maintenance hazard ratio for EGFRmut⁺ was 0.15 (95% CI = 0.08 to 0.27; P < .001), and the maintenance hazard ratio for EGFRmut^– was 0.81 (95% CI = 0.68 to 0.97; P = .02; P_interaction < .001). EGFR-TKIs treatment had no impact on OS for EGFRmut⁺ and EGFRmut^– patients. EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut⁺ patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut⁺ advanced NSCLC patients.

To evaluate lung abnormalities on serial thin-section computed tomographic (CT) scans in patients with severe acute respiratory syndrome (SARS) during acute and convalescent periods. Serial thin-section CT scans in 30 patients (17 men, aged 42.5 years +/- 12.2 [SD]) with SARS were reviewed by two radiologists together for predominant patterns of lung abnormalities: ground-glass opacities, ground-glass opacities with superimposed linear opacities, consolidation, reticular pattern, and mixed pattern (consolidation, ground-glass opacities, and reticular pattern). Scans were classified according to duration in weeks after symptom onset. Longitudinal changes of specific abnormalities were documented in 17 patients with serial scans obtained during 3 weeks. Each lung was divided into three zones; each zone was evaluated for percentage of lung involvement. Summation of scores from all six lung zones provided overall CT score (maximal CT score, 24). Median CT scores increased from 1 in the 1st week to 12.5 in the 2nd week. Ground-glass opacities with or without smooth interlobular septal thickening and consolidation were predominant patterns found during the 1st week. Ground-glass opacities with superimposed irregular reticular opacities, mixed pattern, and reticular opacities were noted from the 2nd week and peaked at or after the 4th week. After the 4th week, 12 (55%) of 22 patients had irregular linear opacities with or without associated ground-glass opacities and CT scores greater than 5; five of these patients had bronchial dilatation. When specific opacities were analyzed in 17 patients, consolidation generally resolved completely (n = 4) or to minimal residual opacities; six (55%) of 11 patients with ground-glass opacities had substantial residual disease (CT scores > 5) on final scans. There is a temporal pattern of lung abnormalities at thin-section CT in SARS. Predominant findings at presentation are ground-glass opacities and consolidation. Reticulation is evident after the 2nd week and persists in half of all patients evaluated after 4 weeks. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.

The increased susceptibility of the elderly to lower respiratory tract infection cannot be fully explained. Although mucociliary clearance, which is affected by ciliary beating and ultrastructure, plays a crucial role in the defense of the airways against inhaled microbes, little is known of the effects of aging on these parameters. We studied the nasal mucociliary clearance (NMCC) time, ciliary beat frequency, and ultrastructure of respiratory cilia in a cohort of healthy volunteers (age range 11 to 90 yr). Ciliary beat frequency of ciliated nasal epithelial cells was obtained via an established photometric method, and NMCC time was measured with the saccharine test. There was a correlation of ciliary beat frequency (r = − 0.48, p = 0.0001) and NMCC time r = 0.64, p < 0.001) with increasing age. Transmission electron microscopy revealed an increase in the percent of subjects exhibiting microtubular disarrangement and single central microtubules with aging (p = 0.002 and p = 0.005, respectively). Subjects older than 40 yr of age had significantly slower ciliary beat frequency, higher percent of ciliary cross-sections displaying single tubules, and longer NMCC time than their younger counterparts (p < 0.05). These findings may help explain the frequent occurrence of respiratory infection in the elderly.

The treatment of atypical pneumonia, subsequently termed severe acute respiratory syndrome (SARS), is controversial, and the efficacy of corticosteroid therapy is unknown. We have evaluated the clinical and radiographic outcomes of 72 patients with probable SARS (median age 37 years, 30 M), who received ribavirin and different steroid regimens in two regional hospitals. Chest radiographs were scored according to the percentage of lung field involved. Seventeen patients initially received pulse steroid (PS) (methylprednisolone ⩾ 500 mg/day) and 55 patients initially received nonpulse steroid (NPS) (methylprednisolone < 500 mg/day) therapy. The cumulative steroid dosage; intensive care unit admission, mechanical ventilation, and mortality rates; and hematologic and biochemical parameters were similar in both groups after 21 days. However, patients in the PS group had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue PS therapy than their counterparts. There was no significant difference between the two groups in hemolytic anemia, severe secondary infections, or hematemesis, but patients in the PS group had less hyperglycaemia. Initial use of pulse methylprednisolone therapy appears to be a more efficacious and an equally safe steroid regimen when compared with regimens with lower dosage and should be considered as the preferred steroid regimen in the treatment of SARS, pending data from future randomized controlled trials.