Patient With Pulmonary Symptoms, Dysphagia, and Raynaud Disease.

A nonsmoking patient with gastroesophageal reflux disease and Raynaud disease had 4 weeks of dysphagia and a 4.54-kg weight loss over 3 months, cough productive of yellow sputum, and dyspnea on exertion. White blood cell count and creatine kinase and aldolase levels were elevated; antinuclear antibody assay findings were positive; and chest CT showed bibasilar pulmonary consolidations and ground glass opacities. What is the diagnosis and what would you do next?

Idiopathic pulmonary fibrosis: Current and future treatment.

OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development. DATA SOURCE: The data were obtained from the Randomized Controlled Trials and scientific studies published in English literature. We used search terms related to IPF, antifibrotic treatment, lung transplant, and management. RESULTS: Etiopathogenesis of IPF is not fully understood, and treatment options are limited. Pathological features of IPF include extracellular matrix remodeling, fibroblast activation and proliferation, immune dysregulation, cell senescence, and presence of aberrant basaloid cells. The mainstay therapies are the oral antifibrotic drugs pirfenidone and nintedanib, which can improve quality of life, attenuate symptoms, and slow disease progression. Unilateral or bilateral lung transplantation is the only treatment for IPF shown to increase life expectancy. CONCLUSION: Clearly, there is an unmet need for accelerated research into IPF mechanisms so that progress can be made in therapeutics toward the goals of increasing life expectancy, alleviating symptoms, and improving well-being.

Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease with high mortality that commonly occurs in middle-aged and older adults. IPF, characterized by a decline in lung function, often manifests as exertional dyspnea and cough. Symptoms result from a fibrotic process driven by alveolar epithelial cells that leads to increased migration, proliferation, and differentiation of lung fibroblasts. Ultimately, the differentiation of fibroblasts into myofibroblasts, which synthesize excessive amounts of extracellular matrix proteins, destroys the lung architecture. However, the factors that induce the fibrotic process are unclear. Diagnosis can be a difficult process; the gold standard for diagnosis is the multidisciplinary conference. Practical biomarkers are needed to improve diagnostic and prognostic accuracy. High-resolution computed tomography typically shows interstitial pneumonia with basal and peripheral honeycombing. Gas exchange and diffusion capacity are impaired. Treatments are limited, although the anti-fibrotic drugs pirfenidone and nintedanib can slow the progression of the disease. Lung transplantation is often contraindicated because of age and comorbidities, but it improves survival when successful. The incidence and prevalence of IPF has been increasing and there is an urgent need for improved therapies. This review covers the detailed cellular and molecular mechanisms underlying IPF progression as well as current treatments and cutting-edge research into new therapeutic targets.

Six-Minute Walk Test: Clinical Role, Technique, Coding, and Reimbursement.

The 6-min walk test (6MWT) is a commonly used test for the objective assessment of functional exercise capacity for the management of patients with moderate-to-severe pulmonary disease. Unlike pulmonary function testing, the 6MWT captures the often coexisting extrapulmonary manifestations of chronic respiratory disease, including cardiovascular disease, frailty, sarcopenia, and cancer. In contrast with cardiopulmonary exercise stress testing, this test does not require complex equipment or technical expertise. In this low complexity, safe test, the patient is asked to walk as far as possible along a 30-m minimally trafficked corridor for a period of 6 min with the primary outcome measure being the 6-min walk distance (6MWD) measured in meters. There has been interest in other derived indexes, such as distance-desaturation product (the product of nadir oxygen saturation and walk distance), which in small studies has been predictive of morbidity and mortality in certain chronic respiratory conditions. Special attention to methodology is required to produce reliable and reproducible results. Factors that can affect walk distance include track layout (continuous vs straight), track length, oxygen amount and portability, learning effect, and verbal encouragement. The absolute 6MWD and change in 6MWD are predictive of morbidity and mortality in patients with COPD, pulmonary arterial hypertension, and idiopathic pulmonary fibrosis and patients awaiting lung transplant, highlighting its use in management decisions and clinical trials. As of January 2018, Current Procedural Terminology code 94620 (simple pulmonary stress test) has been deleted and replaced by two new codes, 94617 and 94618. Code 94617 includes exercise test for bronchospasm including pre- and postspirometry, ECG recordings, and pulse oximetry. Code 94618, pulmonary stress testing (eg, 6MWT), includes the measurement of heart rate, oximetry, and oxygen titration when performed. If 94620 is billed after January 2018 it will not be reimbursed.

Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic intermittent hypoxia in mice.

Chronic intermittent hypoxia (CIH) increases sympathetic tone and respiratory instability. Our previous work showed that chronic hypoxia induces the oxygen-sensing enzyme heme oxygenase-1 (HO-1) within the C1 sympathoexcitatory region and the pre-Bötzinger complex (pre-BötC). We therefore examined the effect of CIH on time course of induced expression of HO-1 within these regions and determined whether the induction of HO-1 correlated with changes in respiratory, sigh frequency, and sympathetic responses (spectral analysis of heart rate) to acute hypoxia (10% O2) during 10 days of exposure to CIH in chronically instrumented awake wild-type (WT) and HO-1 null mice (HO-1-/-). HO-1 was induced within the C1 and pre-BötC regions after 1 day of CIH. There were no significant differences in the baseline respiratory parameters between WT and HO-1-/- Prior to CIH, acute hypoxia increased respiratory frequency in both WT and HO-1-/-; however, minute diaphragm electromyogram activity increased in WT but not HO-1-/- The hypoxic respiratory response after 1 and 10 days of CIH was restored in HO-1-/- CIH resulted in an initial significant decline in 1) the hypoxic sigh frequency response, which was restored in WT but not HO-1-/-, and 2) the baseline sympathetic activity in WT and HO-1-/-, which remained stable subsequently in WT but not in HO-1-/- We conclude that 1) CIH induces expression of HO-1 in the C1 and pre-BötC regions within 1 day and 2) HO-1 is necessary for hypoxia respiratory response and contributes to the maintenance of the hypoxic sigh responses and baseline sympathetic activity during CIH.